32196 hot topic(s) found with the query "All"
Healthcare utilization and behavior changes following workplace genetic testing at a large U.S. healthcare system
(Posted: May 08, 2024 11AM)
From the abstract: " This study explored employee health behavior changes and healthcare utilization following workplace genetic testing (wGT). Wellness program-associated wGT seeks to improve employee health, but related health implications are unknown. Methods: Employees of a large U.S. healthcare system offering wGT (cancer, heart disease, and pharmacogenomics - PGx) were sent electronic surveys. Self-reported data from those who received test results were analyzed. Descriptive statistics characterized responses, while logistic regression analyses explored correlates of responses to wGT."
Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial
(Posted: May 08, 2024 11AM)
From the abstract: "Large variability exists in people’s responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program."
Advancing genomics to improve health equity
(Posted: May 07, 2024 10AM)
From the abstract: " Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. "
APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease
(Posted: May 07, 2024 10AM)
From the abstract: "This study aimed to evaluate the impact of APOE4 homozygosity on Alzheimer’s disease (AD) by examining its clinical, pathological and biomarker changes to see whether APOE4 homozygotes constitute a distinct, genetically determined form of AD. Data from the National Alzheimer’s Coordinating Center and five large cohorts with AD biomarkers were analyzed. The analysis included 3,297 individuals for the pathological study and 10,039 for the clinical study. Findings revealed that almost all APOE4 homozygotes exhibited AD pathology and had significantly higher levels of AD biomarkers from age 55 compared to APOE3 homozygotes. By age 65, nearly all had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans. "
It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States
(Posted: May 07, 2024 10AM)
From the abstract: "Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9–11. "
Equitable implementation of a precision digital health program for glucose management in individuals with newly diagnosed type 1 diabetes
(Posted: May 03, 2024 5PM)
From the abstract: " Few young people with type 1 diabetes (T1D) meet glucose targets. Continuous glucose monitoring improves glycemia, but access is not equitable. We prospectively assessed the impact of a systematic and equitable digital-health-team-based care program implementing tighter glucose targets (HbA1c?<?7%), early technology use (continuous glucose monitoring starts <1?month after diagnosis) and remote patient monitoring on glycemia in young people with newly diagnosed T1D enrolled in the Teamwork, Targets, Technology, and Tight Control (4T Study)."
Rapid pathogen surveillance: field-ready sequencing solutions
(Posted: May 03, 2024 5PM)
From the article: "Genetic sequencing of pathogens has revolutionized the surveillance of infectious diseases, empowering scientists and health officials to anticipate and respond effectively to outbreaks. Despite their transformative potential, next-generation sequencing technologies have traditionally been inaccessible to many in the global scientific community, particularly in the Global South. This is primarily due to the prohibitively high capital costs and a widespread deficiency in laboratory infrastructure and genomics expertise. Ironically, it is in these regions where genomic surveillance could yield the most crucial insights, underscoring the urgent need for equitable access to such transformative technologies. "
The FDA and Gene Therapy for Duchenne Muscular Dystrophy
(Posted: May 01, 2024 5PM)
From the article: " DMD is the largest human gene and has 79 exons. This large size creates issues for gene therapies, but also opportunities, because shortened forms of dystrophin can have some ability to preserve muscle function, although less than the full-length dystrophin protein. A less severe and clinically variable form of muscular dystrophy, Becker muscular dystrophy, is due to alterations in DMD that result in variable levels of expression (5%-50% of normal) of a shortened form of dystrophin."
Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
(Posted: May 01, 2024 5PM)
From the abstract: " Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59?P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia."
Genetic Research within Indigenous Communities: Engagement Opportunities and Pathways Forward
(Posted: May 01, 2024 2PM)
From the abstract: " Against a historical backdrop of researchers who violated trust through lack of benefit sharing, transparency, and engagement, efforts are underway to develop better approaches for genetic and genomic research with Indigenous communities. To increase engagement, there is a need to understand factors that impact researcher and community collaborations. This study aimed to understand the barriers, challenges, and facilitators of Indigenous Peoples in the US participating in genetic research."
Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network
(Posted: May 01, 2024 1PM)
From the abstract: "The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. "
Inequity of genetic screening: DNA tests fail non-white families more often
(Posted: Apr 29, 2024 11AM)
From the article: "DNA sequencing for metabolic diseases in newborns may eventually replace the traditional method of genetic screening used to check all new babies for a group of rare, inherited diseases that can cause severe neurologic damage and death if not detected quickly. But currently, research is showing that those advanced methods of genetic tests aren't equally useful for everyone: They're less accurate for non-white families, raising concerns about how historical gaps in whose DNA gets studied produce inequities in medical care."
Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for pediatric diagnostic testing
(Posted: Apr 29, 2024 11AM)
From the abstract: "Measuring effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents’ perceived utility of pediatric diagnostic GS. Methods: Informed by a five-domain conceptual model, the study comprised five steps: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. "
Polygenic scores for longitudinal prediction of incident type 2 diabetes in an ancestrally and medically diverse primary care physician network: a patient cohort study
(Posted: Apr 29, 2024 11AM)
From the article: "Genetic information, if available, could improve T2D prediction among patients lacking measured clinical risk factors. Genome-wide association studies (GWAS) have identified hundreds of unique loci associated with T2D, the results of which can be used to calculate polygenic scores (PGS) that model genetic risk independently of established clinical risk factors including family history. Previous work has evaluated how PGS can be used within healthcare systems, but analyses have been largely cross-sectional in biobanks of mostly European ancestry, limiting the generalizability of results to a more ancestrally and medically diverse US healthcare system. "
Bird flu virus has been spreading in US cows for months, RNA reveals Genomic analysis suggests that the outbreak probably began in December or January, but a shortage of data is hampering efforts to pin down the source.
(Posted: Apr 29, 2024 11AM)
From the article: "A strain of highly pathogenic avian influenza has been silently spreading in US cattle for months, according to preliminary analysis of genomic data. The outbreak is likely to have begun when the virus jumped from an infected bird into a cow, probably around late December or early January. This implies a protracted, undetected spread of the virus — suggesting that more cattle across the United States, and even in neighbouring regions, could have been infected with avian influenza than currently reported. These conclusions are based on swift and summary analyses by researchers, following a dump of genomic data by the US Department of Agriculture (USDA) into a public repository earlier this week. "
An approach to identify gene-environment interactions and reveal new biological insight in complex traits
(Posted: Apr 25, 2024 9AM)
From the abstract: " Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci (6 independent signals) interacted with either cigarette smoking or alcohol consumption for serum lipids, and empirically demonstrate that interaction and mediation are the major contributors to genetic effect size heterogeneity across populations. "
Aspiring toward equitable benefits from genomic advances to individuals of ancestrally diverse backgrounds
(Posted: Apr 25, 2024 9AM)
From the abstract: "Despite the promise of genomic technologies, their full potential remains untapped without including individuals of diverse ancestries and integrating social determinants of health (SDOHs). The NHGRI launched the 2020 Strategic Vision with ten bold predictions by 2030, including “individuals from ancestrally diverse backgrounds will benefit equitably from advances in human genomics." Meeting this goal requires a holistic approach that brings together genomic advancements with careful consideration to healthcare access as well as SDOHs to ensure that translation of genetics research is inclusive, affordable, and accessible and ultimately narrows rather than widens health disparities. "
Exagamglogene Autotemcel for Severe Sickle Cell Disease
(Posted: Apr 25, 2024 8AM)
From the abstract: "We conducted a phase 3, single-group, open-label study of exa-cel in patients 12 to 35 years of age with sickle cell disease who had had at least two severe vaso-occlusive crises in each of the 2 years before screening. CD34+ HSPCs were edited with the use of CRISPR-Cas9...A total of 44 patients received exa-cel, and the median follow-up was 19.3 months...Treatment with exa-cel eliminated vaso-occlusive crises in 97% of patients with sickle cell disease for a period of 12 months or more. "
Genome-first evaluation with exome sequence and clinical data uncovers underdiagnosed genetic disorders in a large healthcare system
(Posted: Apr 21, 2024 0PM)
From the abstract: "Population-based genomic screening may help diagnose individuals with disease-risk variants. Here, we perform a genome-first evaluation for nine disorders in 29,039 participants with linked exome sequences and electronic health records (EHRs). We identify 614 individuals with 303 pathogenic/likely pathogenic or predicted loss-of-function (P/LP/LoF) variants, yielding 644 observations; 487 observations (76%) lack a corresponding clinical diagnosis in the EHR."
Microbiome-based therapeutics
(Posted: Apr 21, 2024 8AM)
From the article: "The gut microbiome plays an important part in a number of gastrointestinal conditions, including Clostridioides difficile infection and inflammatory bowel disease. Interest in modulating the gut microbiome, through prebiotics, probiotics, and natural or artificial microbiota therapeutics, has increased markedly in the past decade. Although the field has developed rapidly, it has faced reproducibility issues and encountered safety and regulatory hurdles. This two-part Series explores the development and promise of artificial microbiome therapeutics, and the current and future perspectives for microbiota therapies for treating inflammatory bowel disease. "
Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer
(Posted: Apr 21, 2024 8AM)
From the article: "Can a new 18-gene urinary test for high-grade prostate cancer (ie, grade group [GG] 2 or greater) improve prostate-specific antigen (PSA) screening outcomes relative to existing biomarker tests? Findings: In this diagnostic study including 761 men in the development cohort and 743 men in the validation cohort, novel cancer-specific and high-grade cancer-specific genes were identified from RNA sequencing data and optimally modeled in a development cohort, yielding an 18-gene test for high-grade prostate cancer. Applying a testing approach with 95% sensitivity for high-grade prostate cancer to an external validation population, use of the 18-gene test would have reduced the number of unnecessary biopsies performed relative to current guideline-endorsed tests. Meaning: The new 18-gene prostate cancer test may reduce more burdensome additional testing (eg, imaging and biopsy) while maintaining highly sensitive detection of high-grade cancer in patients undergoing PSA screening. "
Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants
(Posted: Apr 21, 2024 8AM)
From the article: "Is postpartum diagnosis an independent risk factor associated with mortality among patients with young-onset breast cancer with germline BRCA1/2 pathogenic variants (PVs)? Findings: This cohort study including 903 women with BRCA germline PVs found that a breast cancer diagnosis less than 10 years post partum was associated with higher risk of mortality compared with nulliparous women and women diagnosed at least 10 years post partum. Increased risk after childbirth varied, with highest risk at less than 5 years for women with ER-positive breast cancer vs 5 to less than 10 years for women with ER-negative breast cancer, and BRCA1 carriers had peak risk of mortality 5 to less than 10 years post partum, with no associations observed for BRCA2 carriers. Meaning: These findings suggest that a breast cancer diagnosis within 10 years of childbirth was independently associated with increased risk for mortality in patients with germline BRCA1/2 PVs, especially for carriers of BRCA1 PVs."
Return of Results in Genomic Research Using Large-Scale or Whole Genome Sequencing: Toward a New Normal
(Posted: Apr 19, 2024 10AM)
From the abstract: "Genome sequencing is increasingly used in research and integrated into clinical care. In the research domain, large-scale analyses, including whole genome sequencing with variant interpretation and curation, virtually guarantee identification of variants that are pathogenic or likely pathogenic and actionable. Multiple guidelines recommend that findings associated with actionable conditions be offered to research participants in order to demonstrate respect for autonomy, reciprocity, and participant interests in health and privacy."
Adherence to the Mediterranean diet can beneficially affect the gut microbiota composition: a systematic review
(Posted: Apr 19, 2024 10AM)
From the abstract: "Dietary patterns could have a notable role in shaping gut microbiota composition. Evidence confirms the positive impact of the Mediterranean diet (MD), as one of the most studied healthy dietary patterns, on the gut microbiota profile. We conducted this systematic review to investigate the results of observational studies and clinical trials regarding the possible changes in the gut microbiota composition, metabolites, and clinical outcomes following adherence to MD in healthy cases or patients suffering from metabolic disorders. "
Impact of Race, Socioeconomic Status, and Geography on Healthcare Outcomes for Children With Sickle Cell Disease in the United States: A Scoping Review
(Posted: Apr 19, 2024 10AM)
From the abstract: "A large proportion of patients with sickle cell disease (SCD) identify as Black or African American (AA). Social bias and stigma in healthcare outcomes for children with SCD are impossible to explore without considering the impact of racial/cultural identity, socioeconomic status (SES), and geography. It is important to understand the current influences of social movements, expanded health insurance coverage, and telehealth on these variables when considering healthcare outcomes for patients with SCD. "
Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial
(Posted: Apr 19, 2024 10AM)
From the abstract: " Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science—including mixed-methods contextual inquiry with clinicians, patients, and health system constituents—to co-design two patient-facing implementation strategies to address this care gap..."
Genetic Researchers' Use of and Interest in Research With Diverse Ancestral Groups.
(Posted: Apr 18, 2024 8AM)
From the article: " Question: Are genetic researchers interested in research with diverse ancestral groups, and how can data stewards encourage that use?
Findings: In this survey study of 294 genetic researchers, significantly more respondents reported working with data from European ancestral populations than any other ancestral population, and European samples were more likely to be considered by researchers as adequate across data-steward type. Most researchers were interested in using more diverse ancestral populations and reported that increasing ancestral diversity of existing databases would enable such research. Meaning: These findings suggest that there are specific gaps in access to and composition of genetic databases, underscoring the need to boost diversity in existing research samples to improve inclusivity in genetic research practices."
Genomic Answers for Kids: Toward more equitable access to genomic testing for rare diseases in rural populations
(Posted: Apr 18, 2024 8AM)
From the abstract: "Next-generation sequencing has revolutionized the speed of rare disease (RD) diagnoses. While clinical exome and genome sequencing represent an effective tool for many RD diagnoses, there is room to further improve the diagnostic odyssey of many RD patients. One recognizable intervention lies in increasing equitable access to genomic testing. Rural communities represent a significant portion of underserved and underrepresented individuals facing additional barriers to diagnosis and treatment."
Expanding Applications of Clinical Genetic Testing - Ethical Challenges.
(Posted: Apr 18, 2024 8AM)
From the article: "Thanks to advances in human genomics, both technological and discovery-based, genetic and genomic testing (which we will refer to collectively as “genetic testing”) are playing an increasingly important role in clinical care. Although genetic testing has long been recognized as raising thorny ethical dilemmas, the widening scope and scale of genetic tests are reshaping old concerns and posing new challenges. Moreover, the need to address these ethical challenges is no longer restricted to clinicians in particular niches, instead becoming immediately relevant for all clinicians. "
Liminality between direct and family-mediated contact in the communication of genetic information to at-risk relatives.
(Posted: Apr 18, 2024 7AM)
From the article: "Ever since genetic test results have been able to be reported, questions have arisen regarding their implications for genetic relatives. Alongside the proband in whom the initial diagnosis is made, family members often also have an interest in the information. Being informed allows an at-risk relative to consider genetic counseling and testing, and to act in advance to prevent or mitigate future morbidity. Indeed, supporting patients to communicate risk information to their relatives is now considered as a key aspect for maximizing the benefits of genomic medicine. "
Precision Medicine—Are We There Yet? A Narrative Review of Precision Medicine’s Applicability in Primary Care
W Evans et al, JPM, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: "Precision medicine (PM) has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review, we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. "
Assessing the Benefits and Harms Associated with Early Diagnosis from the Perspective of Parents with Multiple Children Diagnosed with Duchenne Muscular Dystrophy
O Battacharria et al, IJNS, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: " Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder diagnosed in childhood. Limited newborn screening in the US often delays diagnosis. With multiple FDA-approved therapies, early diagnosis is crucial for timely treatment but may entail other benefits and harms. Using a community-based survey, we explored how parents of siblings with DMD perceived early diagnosis of one child due to a prior child’s diagnosis. We assessed parents’ viewpoints across domains including diagnostic journey, treatment initiatives, service access, preparedness, parenting, emotional impact, and caregiving experience."
Toward clinical exomes in diagnostics and management of male infertility
C Lillepea et al, AJHG, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: "Infertility, affecting ~10% of men, is predominantly caused by primary spermatogenic failure (SPGF). We screened likely pathogenic and pathogenic (LP/P) variants in 638 candidate genes for male infertility in 521 individuals presenting idiopathic SPGF and 323 normozoospermic men in the ESTAND cohort. Molecular diagnosis was reached for 64 men with SPGF (12%), with findings in 39 genes (6%). The yield did not differ significantly between the subgroups with azoospermia (20/185, 11%), oligozoospermia (18/181, 10%), and primary cryptorchidism with SPGF (26/155, 17%). "
Lethal phenotypes in Mendelian disorder
P Cacheiro et al, GIM, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: "We queried Online Mendelian Inheritance in Man for terms related to lethality and classified all Mendelian genes according to the earliest age of death recorded for the associated disorders, from prenatal death to no reports of premature death. We characterised the genes across these lethality categories, examined the evidence on viability from mouse models and explored how this information could be used for novel gene discovery. "
Clinical Application of Different Liquid Biopsy Components in Hepatocellular Carcinoma
J Xu et al, JPM, April 15, 2024
(Posted: Apr 15, 2024 2PM)
From the abstract: "Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, usually occurring in the background of chronic liver disease. HCC lethality rate is in the third highest place in the world. Patients with HCC have concealed early symptoms and possess a high-level of heterogeneity. Once diagnosed, most of the tumors are in advanced stages and have a poor prognosis. The sensitivity and specificity of existing detection modalities and protocols are suboptimal. HCC calls for more sophisticated and individualized therapeutic regimens. Liquid biopsy is non-invasive, repeatable, unaffected by location, and can be monitored dynamically. It has emerged as a useable aid in achieving precision malignant tumor treatment."
International perspectives on measuring national digital public health system maturity through a multidisciplinary Delphi study
L Ma et al, NPJ Digital Medicine, April 12, 2024
(Posted: Apr 12, 2024 9AM)
From the abstract: "Unlocking the full potential of digital public health (DiPH) systems requires a comprehensive tool to assess their maturity. While the World Health Organization and the International Telecommunication Union released a toolkit in 2012 covering various aspects of digitalizing national healthcare systems, a holistic maturity assessment tool has been lacking ever since. To bridge this gap, we conducted a pioneering Delphi study, to which 54 experts from diverse continents and academic fields actively contributed to at least one of three rounds. 54 experts participated in developing and rating multidisciplinary quality indicators to measure the maturity of national digital public health systems. "
Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling
TH Sun et al, Nature Comm, April 12, 2024
(Posted: Apr 12, 2024 9AM)
From the abstract: "Polygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from Medical University Hospital. Logistic regression models assessed polygenic scores’ ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. "
Role of next generation sequencing in diagnosis and management of critically ill children with suspected monogenic disorder
S Bahtia et al, EJHG, April 11, 2024
(Posted: Apr 12, 2024 9AM)
From the abstract: " Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care. The study was conducted at a single tertiary hospital in Northern India. We analyzed 70 children with an illness requiring intensive care and obtained a precise molecular diagnosis in 32 of 70 probands (45.3%) using diverse sequencing techniques such as clinical exome, whole exome, and whole genome. A significant change in clinical outcome was observed in 13 of 32 (40.6%) diagnosed probands with a change in medication in 11 subjects and redirection to palliative care in two subjects."
Reporting guidelines in medical artificial intelligence: a systematic review and meta-analysis
F Kolbinger et al, Comm Med, April 11, 2024
(Posted: Apr 12, 2024 9AM)
From the abstract: "AI reporting guidelines for medical research vary with respect to the quality of the underlying consensus process, breadth, and target research phase. Some guideline items such as reporting of study design and model performance recur across guidelines, whereas other items are specific to particular fields and research stages. Our analysis highlights the importance of reporting guidelines in clinical AI research and underscores the need for common standards that address the identified variations and gaps in current guidelines. Overall, this comprehensive overview could help researchers and public stakeholders reinforce quality standards for increased reliability, reproducibility, clinical validity, and public trust in AI research in healthcare. "
Many roads to a gene-environment interaction.
Kenneth E Westerman et al. Am J Hum Genet 2024 4 (4) 626-635
(Posted: Apr 10, 2024 8AM)
From the abstract: "Despite the importance of gene-environment interactions (GxEs) in improving and operationalizing genetic discovery, interpretation of any GxEs that are discovered can be surprisingly difficult. There are many potential biological and statistical explanations for a statistically significant finding and, likewise, it is not always clear what can be claimed based on a null result. Here, we provide a detailed explanation of five “phenomena,” or data-generating mechanisms, that can lead to nonzero interaction estimates, as well as a discussion of specific instances in which they might be relevant. "
Nucleic acid-based drugs for patients with solid tumours.
Sebastian G Huayamares et al. Nat Rev Clin Oncol 2024 4
(Posted: Apr 10, 2024 8AM)
From the abstract: "The treatment of patients with advanced-stage solid tumours typically involves a multimodality approach (including surgery, chemotherapy, radiotherapy, targeted therapy and/or immunotherapy), which is often ultimately ineffective. Nucleic acid-based drugs, either as monotherapies or in combination with standard-of-care therapies, are rapidly emerging as novel treatments capable of generating responses in otherwise refractory tumours. These therapies include those using viral vectors (also referred to as gene therapies), several of which have now been approved by regulatory agencies, and nanoparticles containing mRNAs and a range of other nucleotides. "
Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates
RH Holm et al, Comm Med, April 9, 2024
(Posted: Apr 10, 2024 8AM)
From the abstract: "We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021–August 2021 in Jefferson County, Kentucky (USA). We show the 64% county vaccination rate translate into about a 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence is a 24-fold increase of infection counts, which correspond to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration have the strongest correlation (r?=?0.95) at 1 week lag."
Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia.
Abebe A Fola et al. Commun Med (Lond) 2024 4 (1) 67
(Posted: Apr 10, 2024 8AM)
From the abstract: "We conducted genomic surveillance of Plasmodium falciparum parasites from the 2018 Malaria Indicator Survey in Zambia, a nationally representative household survey of children under five years of age. We whole-genome sequenced and analyzed 241?P. falciparum genomes from regions with varying levels of malaria transmission across Zambia and estimated genetic metrics that are informative about transmission intensity, genetic relatedness between parasites, and selection. We provide genomic evidence of widespread within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in Zambia. Our analysis reveals country-level clustering of parasites from Zambia and neighboring regions, with distinct separation in West Africa. "
Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial.
Oliver Schwartz et al. JAMA Pediatr 2024 4
(Posted: Apr 09, 2024 8AM)
From the abstract: " Is early diagnosis through newborn screening associated with improved outcomes in infants with spinal muscular atrophy compared to those diagnosed after onset of symptoms? In this nonrandomized controlled trial within the SMARTCARE registry, patients identified by newborn screening showed better motor development with disease-modifying treatments than those who were diagnosed after onset of symptoms. These results offer supporting evidence for the benefit of newborn screening for spinal muscular atrophy. "
Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
J Xin et al, Nature Comm, April 8, 2024
(Posted: Apr 09, 2024 8AM)
From the abstract: "The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD?=?1.99, P?=?1.76?×?10-8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P?=?3.21?×?10-14; 543 patients) and 1.80 (P?=?1.11?×?10-9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. "
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.
Gabrielle Lemire et al. Am J Hum Genet 2024 4
(Posted: Apr 09, 2024 8AM)
From the abstract: "Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). "
Improvement of Variant Reclassification in Genetic Neurodevelopmental Conditions
M Kowanda et al, GIM Open, April 9, 2024
(Posted: Apr 09, 2024 8AM)
From the abstract: " Regular re-evaluation of neurodevelopmental genetic variants can be helpful as relevant variant re-classifications occur frequently and may impact clinical care. Simons Searchlight contributes to the international neurodevelopmental community by systematically reviewing uncertain variants annually and providing reclassified variants to participants, researchers, and ClinVar."
Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics
S Porcari et al, Lancet GE Hepa, May 2024
(Posted: Apr 09, 2024 8AM)
From the abstract: " The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments."
Research biobank participants attitudes towards genetic exceptionalism and health record confidentiality.
Victoria Dortenzio et al. J Community Genet 2024 3
(Posted: Apr 08, 2024 9AM)
From the abstract: "The goals of this study were to determine biobank participants’ attitudes towards genetic exceptionalism and confidentiality and whether those attitudes are related to their preference for return of genetic results. An online questionnaire was distributed to patients with an EHR and email address who had previously enrolled in the BioMe Biobank program. Most participants responded with similar levels of concern in scenarios involving the use of genetic information and other types of health information, suggesting that participants want similar protections for genetic data as other types of sensitive health information, particularly mental health and family history records. "
Consensus reporting guidelines to address gaps in descriptions of ultra-rare genetic conditions.
Ali AlMail et al. NPJ Genom Med 2024 4 (1) 27
(Posted: Apr 08, 2024 9AM)
From the abstract: "Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment of novel genetic conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians and families is unclear. We identified reports published from 2017 to 2021 in 10 genetics journals of novel Mendelian disorders. We adjudicated the quality and detail of the phenotype data via 46 questions pertaining to six priority domains. "
A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals.
Mariela V Jennings et al. EBioMedicine 2024 4 105086
(Posted: Apr 08, 2024 9AM)
From the abstract: " We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B: rs1229984-T, rs2066702-A; ADH1C: rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.g., substance-use, mental health, sleep, immune, cardiovascular, metabolic) from a diverse 23andMe cohort, including European (N = 2,619,939), Latin American (N = 446,646) and African American (N = 146,776) populations to uncover new and perhaps unexpected associations. We found that that polymorphisms in genes encoding alcohol metabolising enzymes affect multiple domains of health beyond alcohol-related behaviours. Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine."
Concerted efforts toward genomic surveillance of viral pathogens in immunocompromised individuals.
Matheus Filgueira Bezerra et al. Lancet Microbe 2024 4
(Posted: Apr 08, 2024 9AM)
From the article: "A recent study underscores the crucial need to closely monitor immunocompromised individuals with prolonged SARS-CoV-2 infections for emerging variants and investigate their phenotypic implications. Sequencing the genomes of the viruses from these cases would marginally elevate the cost in the whole COVID-19 genomic surveillance effort, and many countries with universal health systems could effectively integrate the tracking of prolonged COVID-19 infections in people living with HIV into their primary care programmes. "
Susceptibility to Treatment-Resistant Depression Within Families.
Chih-Ming Cheng et al. JAMA Psychiatry 2024 4
(Posted: Apr 05, 2024 9AM)
From the abstract: " Is the treatment-resistant depression (TRD) phenotype transmitted within a family? This cohort study found that, compared with control individuals match for birth year, sex, and kinship, first-degree-relatives of individuals with TRD had an increased risk of developing TRD and increased suicide mortality. The findings suggest that a family history of TRD might be a clinically significant risk factor for resistance to antidepressant treatment and increased suicide mortality, indicating that combining or altering therapies for depression might be considered instead of monotherapy at an earlier treatment stage. "
Human leukocyte antigen variants associate with BNT162b2 mRNA vaccine response.
Martina Esposito et al. Commun Med (Lond) 2024 4 (1) 63
(Posted: Apr 05, 2024 9AM)
From the abstract: "We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above. Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. "
Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies.
Ariadna Tibau et al. JAMA Oncol 2024 4
(Posted: Apr 05, 2024 9AM)
From the abstract: "What is the validity of the molecular targets and clinical benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the results of pivotal clinical trials? In this cohort study, 50 molecular-targeted drugs covering 84 indications were identified. Using an international grading system to evaluate molecular targetability strength (European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets) and a scale to assess clinical benefit in genome-targeted cancer therapies (European Society for Medical Oncology Magnitude of Clinical Benefit Scale), 24 indications (29%) supported high-benefit genomic-based cancer treatments. The therapeutic benefit grading frameworks used in this study can help stakeholders identify therapies with the greatest clinical potential. "
Strategies to improve implementation of cascade testing in hereditary cancer syndromes: a systematic review
J Chiang et al, NPJ Genomic Medicine, April 5, 2024
(Posted: Apr 04, 2024 9AM)
From the abstract: " Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. This systematic review shows that most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream."
mRNA drug offers hope for treating a devastating childhood disease.
Elie Dolgin et al. Nature 2024 4
(Posted: Apr 04, 2024 9AM)
From the article: " Propionic acidemia is a rare genetic disorder, which affects about one in 100,000 individuals worldwide, arises from mutations in either of two genes that together encode an enzyme necessary for the efficient breakdown of certain protein components. Without this enzyme, cells can’t process some nutrients properly. Results from a small trial of mRNA-3927 indicate that the restoration of enzymatic activity is beneficial. Eight of the 16 participants had experienced life-threatening episodes connected to their impaired metabolism in the year before starting treatment. For those eight, the likelihood of experiencing another such event decreased by an average of 70–80% while taking the therapy. "
Proteome profiling of home-sampled dried blood spots reveals proteins of SARS-CoV-2 infections.
Claudia Fredolini et al. Commun Med (Lond) 2024 4 (1) 55
(Posted: Apr 04, 2024 9AM)
From the abstract: "Our three studies display highly consistent variance of protein levels and share associations of proteins with sex (e.g., MMP3) and age (e.g., GDF-15). Studying seropositive (IgG+) and seronegative (IgG-) donors from the first pandemic wave reveals a network of proteins reflecting immunity, inflammation, coagulation, and stress response. Proteome analysis of volumetric self-sampled DBS facilitates precise analysis of clinically relevant proteins, including those secreted into the circulation or found on blood cells, augmenting previous COVID-19 reports with clinical blood collections. Our population surveys support the usefulness of DBS, underscoring the role of timing the sample collection to complement clinical and precision health monitoring initiatives. "
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-A and HLA-B with anti-epileptic drugs.
Lisanne E N Manson et al. Eur J Hum Genet 2024 4
(Posted: Apr 04, 2024 9AM)
From the abstract: "This guideline outlines the gene-drug interaction of CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate and poor metabolisers, the DPWG recommends lowering the daily dose of phenytoin and adjust based on effect and serum concentration after 7–10 days. For HLA-B*15:02 carriers, the risk of severe cutaneous adverse events associated with phenytoin, carbamazepine, oxcarbazepine, and lamotrigine is strongly increased. For carbamazepine, this risk is also increased in HLA-B*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive patients, the DPWG recommends choosing an alternative anti-epileptic drug. "
Socioecologic Factors and Racial Differences in Breast Cancer Multigene Prognostic Scores in US Women.
Ashwini Z Parab et al. JAMA Netw Open 2024 4 (4) e244862
(Posted: Apr 04, 2024 9AM)
From the abstract: " In this cohort study of 69?139 women with breast cancer, non-Hispanic Black and non-Hispanic American Indian and Alaska Native women were more likely to have tumors with high-risk RSs compared with non-Hispanic White women. For non-Hispanic Black women, area-level socioeconomic position, urban residence, and insurance status mediated 17% of the racial difference in the RSs, and racial differences between non-Hispanic Black and non-Hispanic White women in the RSs were observed only among urban women. These findings suggest that disproportionately aggressive breast tumor biology among non-Hispanic Black women may be partially explained by socioecologic factors."
Newborn screening for Duchenne muscular dystrophy: the perspectives of stakeholders.
Charli Ji et al. Lancet Reg Health West Pac 2024 3 101049
(Posted: Apr 02, 2024 10AM)
From the abstract: "Participants included 50 caregivers and 26 HCPs (68.5% and 53.1% response rate respectively). Most caregivers (40/50, 80%) perceived net benefits of DMD NBS and highlighted an early diagnosis as actionable knowledge, even with the current paucity of disease modifying therapies. This knowledge was valued to enable access to multidisciplinary supportive care (29/50, 58%), clinical trials (27/50, 54%), psychological support (28/50, 56%), inform reproductive planning (27/50, 54%), and facilitate financial planning based on the future needs of their child (27/50, 54%). "
Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.
Mariam Kayle et al. MMWR Morb Mortal Wkly Rep 2024 3 (12) 248-254
(Posted: Apr 02, 2024 10AM)
From the abstract: " Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. "
Challenges and opportunities for Lynch syndrome cascade testing in the United States.
Lauren E Passero et al. Fam Cancer 2024 3
(Posted: Apr 02, 2024 10AM)
From the abstract: " Lynch syndrome is an underdiagnosed genetic condition that increases lifetime colorectal, endometrial, and other cancer risk. Cascade testing in relatives is recommended to increase diagnoses and enable access to cancer prevention services, yet uptake is limited due to documented multi-level barriers. Individual barriers such as feelings of fear, guilt, and anxiety and limited knowledge about Lynch syndrome as well as interpersonal barriers including complex family dynamics and language barriers limit family communication about Lynch syndrome and prevent uptake of genetic screening for relatives. Organizational and environmental barriers including a shortage of genetics professionals, high costs, and fears of discrimination also reduce cascade testing. These multi-level barriers may disproportionately impact underserved populations in the United States,"
Overcoming barriers to single-cell RNA sequencing adoption in low- and middle-income countries
TB Serebour et al, EJHG, April 2, 2024
(Posted: Apr 02, 2024 9AM)
From the abstract: " The advent of single-cell resolution sequencing and spatial transcriptomics has enabled the delivery of cellular and molecular atlases of tissues and organs, providing new insights into tissue health and disease. However, if the full potential of these technologies is to be equitably realised, ancestrally inclusivity is paramount. Such a goal requires greater inclusion of both researchers and donors in low- and middle-income countries (LMICs). In this perspective, we describe the current landscape of ancestral inclusivity in genomic and single-cell transcriptomic studies. We discuss the collaborative efforts needed to scale the barriers to establishing, expanding, and adopting single-cell sequencing research in LMICs."
A framework for the evaluation and reporting of incidental findings in clinical genomic testing
CM Brown et al, EJHG, April 2, 2024
(Posted: Apr 02, 2024 9AM)
From the abstract: "Herein we describe a framework developed to guide the evaluation and return of IFs encountered in probands undergoing clinical genome sequencing (cGS). The framework prioritizes clinical significance and actionability of IFs and follows a stepwise approach with stopping points at which IFs may be recommended for return or not. Over 18 months, implementation of the framework in a clinical laboratory facilitated the return of actionable IFs in 37 of 720 (5.1%) individuals referred for cGS. "
Utilizing geospatial artificial intelligence to map cancer disparities across health regions
A Fadiel et al, Sci Report, April 2, 2024
(Posted: Apr 02, 2024 9AM)
From the abstract: "We have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions. Powered by Artificial Intelligence and Machine Learning, our tool employs a robust Geographic Information System (GIS) to map healthcare outcomes and disease disparities. iCAT allows users to query publicly available data sources, health system data, and treatment data, offering insights into gaps and disparities in diagnosis and treatment paradigms. "
Newborn Screening for Inborn Errors of Metabolism by Next-Generation Sequencing Combined with Tandem Mass Spectrometry
C Tang et al, IJNS, March 2024
(Posted: Apr 02, 2024 9AM)
From the abstract: " We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. "
Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.
Darcy L Fehlings et al. Nat Genet 2024 3
(Posted: Apr 01, 2024 9AM)
From the abstract: " We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes."
Future implications of polygenic risk scores for life insurance underwriting.
Tatiane Yanes et al. NPJ Genom Med 2024 3 (1) 25
(Posted: Apr 01, 2024 9AM)
From the abstract: "As PGS is increasingly utilized in research and clinical practice, it is pivotal that careful consideration is given to the potential insurance implications of PGS to ensure consumer protection against GD. For the full potential benefits of PGS to be realized, and its clinical utility determined across various use cases, individuals will need to be confident that they can participate in research studies and access clinical genetic testing without fear of insurance discrimination. Clarification is needed regarding the extent to which existing protections and legislation relating to monogenic testing may also extend to PGS test results. "
Advancing access to genome sequencing for rare genetic disorders: recent progress and call to action.
Vaidehi Jobanputra et al. NPJ Genom Med 2024 3 (1) 23
(Posted: Apr 01, 2024 9AM)
From the article: "GS has ushered in a new era in the diagnosis of genetic diseases, offering the potential for improved patient care. Now is the time for collective action to overcome challenges, implement best practices, and ensure that the benefits of GS are realized for all individuals affected by genetic diseases. Indeed, widespread and appropriate utilization of GS is critical for directing the emerging gene editing, gene therapy, and cell-based therapies for rare genetic disorders. Concerted policy, education, guideline, and care pathway efforts will drive significant advancements in precision medicine and improve health outcomes for patients with genetic conditions. "
What to Know About Lynch Syndrome
ThedaCare Genetic Counseling, March 2024
(Posted: Apr 01, 2024 9AM)
From the article: " While it is impossible to change our genes, with knowledge comes power. In the case of Lynch syndrome, a genetic condition that can increase a person’s risk for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening, as well as genetic testing, when recommended."
Deep learning in cancer genomics and histopathology
M Unger et al, Genome Medicine, March 27, 2024
(Posted: Mar 27, 2024 1PM)
From the abstract: " Histopathology and genomic profiling are cornerstones of precision oncology and are routinely obtained for patients with cancer. Traditionally, histopathology slides are manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated by engineered computational pipelines. In both applications, the advent of modern artificial intelligence methods, specifically machine learning (ML) and deep learning (DL), have opened up a fundamentally new way of extracting actionable insights from raw data, which could augment and potentially replace some aspects of traditional evaluation workflows. "
Applications of genome sequencing as a single platform for clinical constitutional genetic testing
Y Yang et al, GIM Open, March 20, 2024
(Posted: Mar 27, 2024 1PM)
From the abstract: "The number of human disease genes has dramatically increased over the past decade, largely fueled by ongoing advances in sequencing technologies. In parallel, the number of available clinical genetic tests has also increased, including exome sequencing for undiagnosed diseases. Although most clinical sequencing tests have been centered on enrichment-based multigene panels and exome sequencing, the continued improvements in performance and throughput of genome sequencing suggest that this technology is emerging as a potential platform for routine clinical genetic testing. "
Advancing Newborn Screening Long-Term Follow-Up: Integration of Epic-Based Registries, Dashboards, and Efficient Workflows
K Raboin et al, IJNS, March 25, 2024
(Posted: Mar 27, 2024 1PM)
From the abstract: "The Connecticut Newborn Screening (NBS) Network, in partnership with the Connecticut Department of Public Health, strategically utilized the Epic electronic health record (EHR) system to establish registries for tracking long-term follow-up (LTFU) of NBS patients. After launching the LTFU registry in 2019, the Network obtained funding from the Health Resources and Services Administration to address the slow adoption by specialty care teams. "
Amyotrophic lateral sclerosis: translating genetic discoveries into therapies.
Fulya Akçimen et al. Nat Rev Genet 2023 4 (9) 642-658
(Posted: Mar 27, 2024 1PM)
From the abstract: "Recent advances in sequencing technologies and collaborative efforts have led to substantial progress in identifying the genetic causes of amyotrophic lateral sclerosis (ALS). This momentum has, in turn, fostered the development of putative molecular therapies. In this Review, we outline the current genetic knowledge, emphasizing recent discoveries and emerging concepts such as the implication of distinct types of mutation, variability in mutated genes in diverse genetic ancestries and gene–environment interactions. "
Pregnancy advances your 'biological' age - but giving birth turns it back.
Saima Sidik et al. Nature 2024 3
(Posted: Mar 25, 2024 9AM)
From the article: " DNA-methylation patterns can be used to estimate a person’s ‘biological age’, which reflects the physiological stresses that a person’s body has accrued over time. Some research has found that biological age is a better predictor of health problems such as cardiovascular disease3 and dementia4 than a person’s chronological age. Pregnancy may lead to changes in the distribution of certain chemical markers on a pregnant person’s DNA — changes similar to those that are a hallmark of getting older. But new research shows that, several months after a person gives birth, the chemical patterns revert to an earlier state. The results strengthen previous preliminary results in humans. "
Secondary use of genomic data: patients’ decisions at point of testing and perspectives to inform international data sharing
M Martyn et al, EJHG, March 25, 2024
(Posted: Mar 25, 2024 8AM)
From the abstract: "International sharing of genomic data files arising from clinical testing of patients is essential to further improve genomic medicine. Whilst the general public are reluctant to donate DNA for research, the choices patients actually make about sharing their clinical genomic data for future re-use (research or clinical) are unknown. We ascertained the data-sharing choices of 1515 patients having genomic testing for inherited conditions or cancer treatment from clinical consent forms. "
DNA test says it can predict opioid addiction risk. Skeptics aren’t so sure.
D Ovalle, Washington Post, March 25, 2024
(Posted: Mar 25, 2024 8AM)
From the article: " Using a swab inside the cheek and a sophisticated computer algorithm, a DNA test recently approved by federal regulators promises to assess genetic risk of opioid addiction. The test’s maker says results give doctors and patients a crucial tool when considering use of the very pain pills that ignited the nation’s opioid crisis. Some geneticists and public health experts say the test relies on unsound science."
Evaluation of a two-step model of opportunistic genomic screening
M Martyn et al, EJHG, March 25, 2024
(Posted: Mar 25, 2024 8AM)
From the abstract: "Increasing use of diagnostic genomic sequencing is pushing health services to confront the issue of opportunistic genomic screening (OGS). To date, OGS has been offered concomitant with diagnostic testing. In contrast, we piloted a service offering OGS after return of diagnostic testing results. Evaluation was designed to provide insights for future models of service and included patient surveys at three time points, semi-structured interviews with genetic counsellors (GCs) and a focus group with medical scientists. Uptake was relatively low: 83 of 200 patients approached (42%) attended the OGS service, with 81 accepting OGS. "
How to support the transition to AI-powered healthcare.
et al. Nat Med 2024 3 (3) 609-610
(Posted: Mar 25, 2024 8AM)
From the article: "To make health systems more sustainable in the long-term, incentivize artificial intelligence (AI) and digital technologies that are grounded on careful testing and real-world validation. We are confident that this transition to ‘AI-powered’ healthcare will occur and that it has the potential to bring widespread public good. At the same time, we believe that these benefits will realize more steadily and more quickly with carefully designed clinical studies and evidence-based implementation of AI algorithms and devices in the real world."
PARP Inhibitors for Breast Cancer Treatment: A Review.
Stefania Morganti et al. JAMA Oncol 2024 3
(Posted: Mar 23, 2024 6AM)
From the abstract: "Poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients. This narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents. Recent studies have shown that the benefit of PARP inhibitors extends beyond patients with germline BRCA1/2-associated metastatic breast cancer to patients with somatic BRCA1/2 variants and to those with germline PALB2 alterations. "
Genomic analysis of 116 autism families strengthens known risk genes and highlights promising candidates
M Viggiano et al, NPJ Genomic Medicine, March 22, 2024
(Posted: Mar 23, 2024 6AM)
From the abstract: "Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in the cases (n?=?144). "
Lynch Syndrome Ups Risk for Colorectal, Other Cancers
E Herlache, Cancer Care, March 2024
(Posted: Mar 23, 2024 6AM)
From the article: "It’s impossible to change our genes, but with knowledge comes power. In the case of Lynch syndrome, a genetic condition that ups people’s risks for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening as well as genetic testing, when warranted. Lynch syndrome puts a person at a higher risk of developing colorectal, uterine, and ovarian cancer. It’s also associated with other cancers, including kidney, stomach, bladder, brain, prostate, and pancreatic cancer. "
The DTC microbiome testing industry needs more regulation.
Diane E Hoffmann et al. Science 2024 3 (6688) 1176-1179
(Posted: Mar 23, 2024 6AM)
From the article: "A growing body of research has suggested the potential for improving human health by better understanding the human microbiome. This research has led to the emergence of a global industry selling direct-to-consumer (DTC) microbiome testing services. Regulation of this industry has been generally ignored despite its having made a mark on the lifestyle health and wellness market. Yet companies’ claims of having the ability to detect “abnormal” microbiomes are not substantiated by research; the testing processes lack analytical validity, and the results have no demonstrated clinical validity. "
Emerging Opportunities for Genomics to Improve Population Health: Lessons learned from the National Academies Roundtable on Genomics and Precision Health
CDC Webinar, May 22, 2024
(Posted: Mar 21, 2024 1PM)
From the website: " For nearly two decades, the National Academies of Sciences, Engineering, and Medicine’s Roundtable on Genomics and Precision Health has brought together diverse voices to share in dialogue about emerging topics in genomics and precision health. Through its public workshops and proceedings of those workshops, the roundtable seeks to encourage innovation and actions that foster the wide adoption of and equitable access to the benefits of genomics and precision health. The webinar will shed light on the emerging opportunities and challenges for genomics to improve population health. The webinar participants will also discuss the role of public health at state and federal levels in fulfilling the promise of genomics and precision health for all. Specific topics relevant to public health practice will be explored."
Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.
Vivienne Souter et al. Circ Genom Precis Med 2024 3 e004457
(Posted: Mar 21, 2024 7AM)
From the abstract: "Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P/LP) variants in the LDLR gene in female individuals receiving reproductive carrier screening. This retrospective observational study included samples from female patients (aged 18–55 years) receiving a 274-gene carrier screening panel. P/LP LDLR variants were identified in 283 samples (1 in 324). No patients were identified with >1 P/LP variant. LDLR carrier frequency was higher in Asian (1 in 191 [95% CI, 1 in 142–258]) compared with White (1 in 417 [95% CI, 1 in 326–533]; P<0.001) or Black groups (1 in 508 [95% CI, 1 in 284–910]; P=0.004). "
The promise of AI in personalized breast cancer screening: are we there yet?
Despina Kontos et al. Nat Rev Clin Oncol 2024 3
(Posted: Mar 21, 2024 7AM)
From the abstract: " The benefits and potential harms of mammography-based screening for breast cancer are often a matter of debate. Here, I discuss the promises and limitations of a recent study that tested an artificial intelligence-based tool for the detection of breast cancer in digital mammograms in a large, prospective screening setting."
Identification of dynamic microbiota signatures in patients with melanoma receiving ICIs: opportunities and challenges.
Saman Maleki Vareki et al. Nat Rev Clin Oncol 2024 3
(Posted: Mar 21, 2024 7AM)
From the abstract: "The composition of the gut microbiota has emerged as a tumour-extrinsic factor that modulates response to immune-checkpoint inhibitors (ICIs), although the lack of consistency in microbiota signatures across studies has limited their value as reliable biomarkers. Herein, we discuss a recent study in which longitudinal microbiome profiling identified several taxa that are persistently enriched in patients with melanoma and a favourable response to ICIs. "
Population Screening for Hereditary Hemochromatosis
Video Webinar, UNC Precision Public Health Network,
(Posted: Mar 20, 2024 7AM)
From the website: " Current data suggest that 1 in 300 non-Hispanic White individuals in the United States carry a genetic variation in the HFE gene (C282Y homozygosity) that accounts for most cases of hereditary hemochromatosis (HH). This variation can lead to iron overload and life-threatening complications, such as severe liver disease. However, complications are preventable with early diagnosis and periodic phlebotomies to remove excess iron from the body. In this CDC webinar, speakers discussed how knowledge about HH has evolved since the discovery of the HFE gene in 1997, current opportunities for clinical and public health action to prevent disease, and future research priorities to advance case detection and reduce clinical complications from HH. "
Training Institute for Dissemination and Implementation Research in Genomics and Precision Public Health (TIDR-GPPH)
UNC Precision Public Health Network, March 2024
(Posted: Mar 20, 2024 7AM)
From the website: "This facilitated course is intended to provide participants with a thorough grounding in conducting dissemination and implementation (D&I) research with a specific focus on genomics and precision public health.is. TIDIR-GPPH will be a hybrid course including training through open access Training Institute for Dissemination and Implementation Research in Cancer (TIDIRC) with assigned reading material and office hours and a 2-day in-person event. Faculty and guest lecturers consist of leading experts in D&I theories, models, and frameworks; intervention fidelity and adaptation; stakeholder engagement and partnership for D&I; research methods and study designs for D&I; and measures and outcomes for D&I. "
Genetics Visit Uptake Among Individuals Receiving Clinically Actionable Genomic Screening Results.
Marci L B Schwartz et al. JAMA Netw Open 2024 3 (3) e242388
(Posted: Mar 18, 2024 3PM)
From the abstract: "What factors are associated with completion of a genetics visit in a population with positive genomic screening results? In this cohort study of a population genomic screening program including 1160 participants, several demographic and program-level factors were associated with the likelihood of completing a follow-up genetics visit. Desire to follow-up with primary care was the most frequently reported reason for declining to schedule a genetics visit.
These findings suggest genomic screening programs may be more successful at supporting patients and clinicians in translating genetic results into clinical action by providing a framework for care coordination among primary care practitioners, genetics clinicians, and specialists."
Recognition of Genetic Conditions After Learning With Images Created Using Generative Artificial Intelligence.
Rebekah L Waikel et al. JAMA Netw Open 2024 3 (3) e242609
(Posted: Mar 18, 2024 3PM)
From the abstract: " In this comparative effectiveness study, generative methods were used to create images of fake but realistic-appearing individuals with Kabuki and Noonan syndrome. Through online surveys, generated images were found to help residents recognize these syndromes and improved their confidence in this area compared with text-only descriptions, although real images were most helpful. These findings suggest that generative artificial intelligence could supplement genetics education for pediatric residents by helping teach the recognition of rare conditions. "
Researchers one step closer to preventing preeclampsia
Medical XPress, APA, March 14, 2024
(Posted: Mar 18, 2024 3PM)
From the website: "Researchers have identified several differences in DNA methylation in people who experienced preeclampsia during pregnancy, according to a new study from Oregon Health & Science University. The study also revealed these differences appear to occur in connection to genes relevant to the disease. "
Prenatal Genome-Wide Sequencing analysis (Exome or Genome) in detecting pathogenic Single Nucleotide Variants in fetal Central Nervous System Anomalies: systematic review and meta-analysis.
Enrica Marchionni et al. Eur J Hum Genet 2024 3
(Posted: Mar 18, 2024 9AM)
From the abstract: "Prenatal Exome (pES) or Genome (pGS) Sequencing analysis showed a significant incremental diagnostic yield over karyotype and chromosomal microarray analysis (CMA) in fetal structural anomalies. Optimized indications and detection rates in different fetal anomalies are still under investigation. The aim of this study was to assess the incremental diagnostic yield in prenatally diagnosed Central Nervous System (CNS) anomalies. Meta-analysis showed a substantial diagnostic improvement in performing Prenatal Genome-Wide Sequencing analysis (Exome or Genome) over karyotype and CMA in CNS anomalies. "
Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.
Marije A van der Geest et al. Eur J Hum Genet 2024 3
(Posted: Mar 18, 2024 9AM)
From the abstract: "In total, we identified nine ELSI aspects, such as (perceived) professional responsibilities, implications for consent and cost-effectiveness. The identified ELSI aspects brought forward necessary trade-offs for GHPs to consciously take into account when considering responsible implementation of systematic reanalysis of NGS data in routine diagnostics, balancing the various strains on their laboratories and personnel while creating optimal results for new and former patients. "
Improved measurement of disease progression in people living with early Parkinson's disease using digital health technologies.
Matthew D Czech et al. Commun Med (Lond) 2024 3 (1) 49
(Posted: Mar 18, 2024 9AM)
From the abstract: "Digital health technologies show promise for improving the measurement of Parkinson’s disease in clinical research and trials. However, it is not clear whether digital measures demonstrate enhanced sensitivity to disease progression compared to traditional measurement approaches. We develop a wearable sensor-based digital algorithm for deriving features of upper and lower-body bradykinesia and evaluate the sensitivity of digital measures to 1-year longitudinal progression using data from the WATCH-PD study, a multicenter, observational digital assessment study in participants with early, untreated Parkinson’s disease. "
Genomes in clinical care
O Riess et al, NPJ Genomic Medicine, March 14, 2024
(Posted: Mar 18, 2024 9AM)
From the abstract: "In the era of precision medicine, genome sequencing (GS) has become more affordable and the importance of genomics and multi-omics in clinical care is increasingly being recognized. However, how to scale and effectively implement GS on an institutional level remains a challenge for many. Here, we present Genome First and Ge-Med, two clinical implementation studies focused on identifying the key pillars and processes that are required to make routine GS and predictive genomics a reality in the clinical setting. "
Cell-free DNA for Colorectal Cancer Screening.
Y M Dennis Lo et al. N Engl J Med 2024 3 (11) 1047-1050
(Posted: Mar 14, 2024 10AM)
From the article: "A recent study demonstrated the feasibility of using plasma cfDNA to screen for colorectal cancer, but the relatively low sensitivity for the detection of advanced precancerous lesions is a limitation. Moreover, colonoscopy not only detects such lesions with high sensitivity but also permits their immediate removal. The noninvasiveness (relatively speaking) of the plasma cfDNA assay, though, is a feature that seems likely to result in greater uptake than colonoscopy."
Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening.
Thomas F Imperiale et al. N Engl J Med 2024 3 (11) 984-993
(Posted: Mar 14, 2024 10AM)
From the abstract: "In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. "
Improving Noninvasive Colorectal Cancer Screening.
John M Carethers et al. N Engl J Med 2024 3 (11) 1045-1046
(Posted: Mar 14, 2024 10AM)
From the article: "Screening for colorectal cancer saves lives. Screening tests have evolved to include stool-based, endoscopic and image-based, and blood-based methods, with minimal thresholds for sensitivity and specificity for colorectal cancer set by the baseline characteristics of FIT. Although multiple tests have been developed over time and vary in cost-effectiveness for colorectal cancer screening, the best screening test is the one that gets completed by the patient. Most of the recommended tests, including the two newer tests assessed in the studies now published in the Journal, improve on the sensitivity and approach the specificity of FIT. "
A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.
Daniel C Chung et al. N Engl J Med 2024 3 (11) 973-983
(Posted: Mar 14, 2024 10AM)
From the abstract: "We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. This cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions."
