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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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290 hot topic(s) found with the query "Obesity"

Distilling causality between physical activity traits and obesity via Mendelian randomization.
Zhe Wang et al. Commun Med (Lond) 2023 11 (1) 173 (Posted: Dec 02, 2023 8AM)

From the abstract: "Whether obesity is a cause or consequence of low physical activity levels and more sedentary time has not yet been fully elucidated. Better instrumental variables and a more thorough consideration of potential confounding variables that may influence the causal inference between physical activity and obesity are needed. This MR study highlights the beneficial effect of education on improved health and suggest that a more physically active lifestyle leads to lower BMI, while sedentary behavior is a consequence of higher BMI."

Association Between a First-Degree Family History and Self-Reported Personal History of Obesity, Diabetes, and Heart and Blood Conditions: Results From the All of Us Research Program.
Danielle Rasooly et al. J Am Heart Assoc 2023 11 e030779 (Posted: Nov 13, 2023 8PM)

From the abstract: "We assessed the association between a self-reported family history of ODHBs and their risk in the adult population (age =20 years) of the AoU (All of Us) Research Program, a longitudinal cohort study of diverse participants across the United States. We conducted a family history-wide association study to systematically assess the association of a first-degree family history of 15 ODHBs in AoU. We use the FamWAS method to estimate 225 familial associations among 15 ODHBs. The results include overlapping associations between family history of different types of cardiometabolic conditions (such as type 2 diabetes and coronary artery disease), and their risk factors (obesity, hypertension), where adults with a family history of 1 ODHB exhibited 1.1 to 5.6 times (1.5, on average) the odds of having a different ODHB. "

Expanding the genetic landscape of obesity.
Jian Yang et al. Cell Genom 2023 9 (9) 100400 (Posted: Nov 10, 2023 7AM)

From the paper: "A recent study epresents a significant advance in our understanding of the genetic architecture of obesity. The identification of sex- and age-specific genetic effects on obesity highlights the importance of considering these factors in future genetic studies, which can help uncover additional genetic factors contributing to disease susceptibility and improve our understanding of the interplay between genetic and environmental factors in disease development. "

Rare Variants of Obesity-Associated Genes in Young Adults with Abdominal Obesity
A Bairkdar et al, JPM, October 16, 2023 (Posted: Oct 17, 2023 9AM)

From the abstract: " In our study, all of the 203 young adults with abdominal obesity had some rare variant in the genes associated with obesity. The widest range of rare and common variants was presented in ADIPOQ, FTO, GLP1R, GHRL, and INS genes. The use of targeted sequencing and clinical criteria makes it possible to identify carriers of rare clinically significant variants in a wide range of obesity-associated genes and to investigate their influence on phenotypic manifestations of abdominal obesity."

Precision medicine of obesity as an integral part of type 2 diabetes management – past, present, and future
L Szczerbinski et al. The Lancet Diabetes Endocr, October 4, 2023 (Posted: Oct 06, 2023 8AM)

From the abstract: " In this Review, we discuss advances in the genetics of obesity from the past decade—with emphasis on developments from the past 5 years—with a focus on metabolic consequences, and their potential implications for precision management of the disease. We also provide an overview of the potential role of genetics in guiding weight loss strategies. Finally, we propose a vision for the future of precision obesity management."

Epigenetics of Early-Life Socioeconomic Stressors and the Impact on Childhood Body Mass Index—Potential Mechanism and Biomarker?
UP Gujral et al, JAMA Pediatrics, September 5, 2023 (Posted: Sep 05, 2023 1PM)

From the paper: "a recent study indicates that salivary epigenetics, an easy measure to obtain in field or clinic, can be used to further explore the questions of pediatric obesity and related outcomes. Epigenetic and physiological BMI may be present at birth and remain stable throughout childhood and adolescence. These findings also add further evidence to a critical window, that of early life, at which to intervene to prevent childhood and adolescent obesity."

CKD Risk Factors
CDC, June 2023 Brand (Posted: Jul 01, 2023 4PM)

Diabetes and high blood pressure are the more common causes of CKD in most adults. Other risk factors include heart disease, obesity, a family history of CKD, inherited kidney disorders, past damage to the kidneys, and older age.

Antagonizing the Leptin Receptor in Obesity.
Clifford J Rosen et al. N Engl J Med 2023 6 (24) 2291-2293 (Posted: Jun 15, 2023 8AM)

Childhood obesity is a challenging clinical condition. Secondary causes of obesity are often sought but rarely found, and few can be addressed by successful therapeutic interventions. Leptin was once hailed as a treatment for most cases of childhood obesity but quickly lost favor when resistance to leptin was noted.

Genetics, genomics, and diet interactions in obesity in the Latin American environment.
Patricia Guevara-Ramírez et al. Frontiers in nutrition 2022 12 1063286 (Posted: Mar 02, 2023 10AM)

Beyond genetic screening-functionality-based precision medicine in monogenic obesity.
Antje Körner et al. The lancet. Diabetes & endocrinology 2023 2 (3) 143-144 (Posted: Feb 28, 2023 7AM)

Most genes causing monogenic obesity are implicated in the central energy regulatory circuits of the leptin-melanocortin pathway. Even though monogenic obesity is still a rare disease entity, identifying these patients is important since there are now promising treatment options such as setmelanotide, a melanocortin receptor agonist, which was recently approved by the US Food and Drug Administration and European Medicines Agency

Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial
R Waziry et al, Nature Aging, February 9, 2023 (Posted: Feb 13, 2023 10AM)

Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n?=?220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2?yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health.

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
S Yojoshi et al, MEDRXIV, January 31, 2023 (Posted: Feb 01, 2023 6AM)

How our microbiome is shaped by family, friends and even neighbours.
Callaway Ewen et al. Nature 2023 1 (Posted: Jan 21, 2023 6AM)

People living in the same household share more than just a roof (and pints of milk). Be they family or flatmate, housemates tend to have the same microbes colonizing their bodies, and the longer the cohabitation, the more similar these microbiomes become. The conclusion — based on a new study of the gut and mouth microbiomes of thousands of people from around the world1 — raises the possibility that diseases linked to microbiome dysfunction, including cancer, diabetes and obesity, could be partly transmissible.

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium
B Moal et al, PLOS ONE, Jan 4, 2023 (Posted: Jan 05, 2023 5AM)

Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).

Genomics and phenomics of body mass index reveals a complex disease network.
Huang Jie et al. Nature communications 2022 12 (1) 7973 (Posted: Jan 02, 2023 0PM)

Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms phenotypes across many organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems.

Assessment of Body Mass Index, Polygenic Risk Score, and Development of Colorectal Cancer.
Chen Xuechen et al. JAMA network open 2022 12 (12) e2248447 (Posted: Dec 23, 2022 6PM)

Do associations of excess weight with development of colorectal cancer differ by polygenic risk for colorectal cancer (CRC)? In this case-control study including 9169 participants (5053 CRC cases, 4116 controls), associations of excess weight with risk of CRC were independent of polygenic risk for CRC. The association of obesity with CRC risk was equivalent to that of having a 41-percentiles higher polygenic risk score. The findings of this study could contribute to enhanced quantification and communication of the association of excess weight with CRC.

DNA Methylation Implicated in Human Obesity and Diabetes
ME Tucker, Medscape, November 2022 (Posted: Nov 14, 2022 6AM)

Previous attempts to identify causal associations between DNA methylation and both obesity and type 2 diabetes have been hindered by challenges in collecting and isolating cells from human tissue. Recent data suggest that manipulation of DNA methylation enzymes in adipocytes can induce or prevent obesity and type 2 diabetes through cellular effects on energy expenditure and insulin sensitivity.

Fitbit step counts clarify the association between activity and chronic disease risk
Nature Medicine, October 11, 2022 (Posted: Oct 12, 2022 8AM)

Using electronic health records data from the All of Us Research Program, we show that higher daily step counts in data collected over several years of Fitbit fitness tracker use were associated with lower risk of common, chronic diseases, including diabetes, hypertension, gastroesophageal reflux disease, depression, obesity and sleep apnea.

Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity
NC Penny et al, Comm Medicine, October 7, 2022 (Posted: Oct 08, 2022 7AM)

Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D.

Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19
J Xie et al, JAMA Internal Medicine, August 18, 2022 (Posted: Aug 18, 2022 1PM)

What is the 30-day acute risk of venous thromboembolism (VTE) among ambulatory patients with COVID-19, and what are the clinical and genetic risk factors predisposing them to developing post–COVID-19 VTE? In this retrospective cohort study of 18?818 outpatients with COVID-19 and 93?179 propensity score–matched noninfected participants, a higher VTE incidence was observed in the former (hazard ratio, 21.42); however, this risk was considerably attenuated among the fully vaccinated, after breakthrough infection. Older age, male sex, obesity, no vaccination or partial vaccination, and inherited thrombophilia were independent risk factors for COVID-19–associated VTE.

Predicting chronic morbidity in childhood cancer survivors.
Vrooman Lynda M et al. Nature medicine 2022 8 (Posted: Aug 09, 2022 7AM)

Approximately 85% of children diagnosed with cancer will be cured of their primary cancer, but epidemiologic and clinical studies have characterized a significant burden of morbidity, as well as excess early mortality, in survivors. Two recent studies show that incorporating genetic factors into risk models improves the prediction of severe obesity for survivors of childhood cancer, which could promote early interventions and better long-term care.

Genetic risk score enhances the risk prediction of severe obesity in adult survivors of childhood cancer.
Sapkota Yadav et al. Nature medicine 2022 7 (Posted: Jul 26, 2022 7AM)

We show the contribution of genetic risk scores (GRSs) to increase prediction of those survivors of childhood cancer who are at risk for severe obesity (body mass index =40?kg?m-2) as an adult. Among 2,548 individuals of European ancestry from the St. Jude Lifetime Cohort Study who were 5-year survivors of childhood cancer, the GRS was found to be associated with 53-fold-higher odds of severe obesity. Addition of GRSs to risk prediction models based on cancer treatment exposures and lifestyle factors significantly improved model prediction (area under the curve increased from 0.68 to 0.75, resulting in the identification of 4.3-times more high-risk survivors).

Risk Factors for COVID-19 Mortality in Pediatric Populations: A Scoping Review
J Theophillia et al, Research Square, June 10, 2022 (Posted: Jun 13, 2022 7AM)

Searches generated a total of 5787 papers and, 78 papers were eligible for analysis. There was a pooled total of 837 pediatric deaths. The presence of at least one comorbidity was a major risk factor; malignancies, cardiovascular diseases and overweight/obesity were the most frequently associated with mortality. The development of Pediatric Multisystem Inflammatory Syndrome (PMIS) was also consistently demonstrated to be a risk factor.

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
S Yojishi et al, MEDRXIV, June 8, 2022 (Posted: Jun 09, 2022 6AM)

Integration of rare expression outlier-associated variants improves polygenic risk prediction
C Smail et al, AJHG, May 18, 2022 (Posted: May 19, 2022 10AM)

Polygenic risk scores (PRSs) quantify the contribution of multiple genetic loci to an individual’s likelihood of a complex trait or disease. However, existing PRSs estimate this likelihood with common genetic variants, excluding the impact of rare variants. Here, we report on a method to identify rare variants associated with outlier gene expression and integrate their impact into PRS predictions for body mass index (BMI), obesity, and bariatric surgery. Between the top and bottom 10%, we observed a 20.8% increase in risk for obesity (p = 3 × 10-14), 62.3% increase in risk for severe obesity (p = 1 × 10-6), and median 5.29 years earlier onset for bariatric surgery (p = 0.008), as a function of expression outlier-associated rare variant burden when controlling for common variant PRS.

Hospitalizations of Children Aged 5–11 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 2020–February 2022
DS Shi et al, MMWR, April 19, 2022 (Posted: Apr 20, 2022 9AM)

COVID-19 can cause severe illness in children. Children aged 5–11 years became eligible for COVID-19 vaccination on November 2, 2021. During the period of Omicron predominance (December 19, 2021–February 28, 2022), COVID-19–associated hospitalization rates in children aged 5–11 years were approximately twice as high among unvaccinated as among vaccinated children. Non-Hispanic Black children represented the largest group of unvaccinated children. Thirty percent of hospitalized children had no underlying medical conditions, and 19% were admitted to an intensive care unit. Children with diabetes and obesity were more likely to experience severe COVID-19.

Chronic Kidney Disease Basics
CDC, March 2022 Brand (Posted: Mar 15, 2022 7AM)

Kidney diseases are a leading cause of death in the United States. About 37 million US adults are estimated to have CKD, and most are undiagnosed. 40% of people with severely reduced kidney function (not on dialysis) are not aware of having CKD. Talk to your doctor about getting tested if you have any of these risk factors: Diabetes, High blood pressure, Heart disease, Family history of CKD, Obesity.

Applying implementation science to improve care for familial hypercholesterolemia.
Jones Laney K et al. Current opinion in endocrinology, diabetes, and obesity 2021 11 (2) 141-151 (Posted: Mar 14, 2022 7AM)

Improving care of individuals with familial hypercholesteremia (FH) is reliant on the synthesis of evidence-based guidelines and their subsequent implementation into clinical care. This review describes implementation strategies, defined as methods to improve translation of evidence into FH care, that have been mapped to strategies from the Expert Recommendations for Implementing Change (ERIC) compilation. There were only 8 of 37 studies that utilized an implementation science theory, model, or framework and two that explicitly addressed health disparities or equity.

Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease
JE Horowitz et al, Nature Genetics, March 4, 2022 (Posted: Mar 04, 2022 7AM)

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which enters human host cells via angiotensin-converting enzyme 2 (ACE2). COVID-19 ranges from asymptomatic infection to severe disease, including respiratory failure and death, and has led to more than 5 million deaths worldwide since December 20195. Reported risk factors for severe COVID-19 include male sex, older age, ethnicity, obesity and cardiovascular and respiratory diseases6,7,8, among others. Host genetic factors have also been shown to modulate the risk of infection and disease severity9,10,11,12. The largest human genetics study performed so far included data from 49,562 individuals infected with SARS-CoV-2 and >1.7 million individuals with no record of infection as controls, and identified 13 independent common risk variants12, many located in or near immune-related genes.

Clinical Characterization of Copy Number Variants Associated With Neurodevelopmental Disorders in a Large-scale Multiancestry Biobank.
Birnbaum Rebecca et al. JAMA psychiatry 2022 1 (3) 250-259 (Posted: Mar 03, 2022 8AM)

In this series of phenotypic association analyses including data from 24 877 individuals, the overall prevalence of NDD CNVs in the biobank was found to be 2.5%. NDD CNV carriers were enriched for congenital disorders and major depressive disorder, and the presence of NDD CNVs was found to be associated with several medical outcomes, including hypertension, obesity, and obesity-related phenotypes, specifically obstructive sleep apnea and increased body mass index.

Microbiome and metabolome features of the cardiometabolic disease spectrum
S Fromentin et al, Nature Medicine, February 17, 2022 (Posted: Feb 18, 2022 8AM)

We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with ischemic heart disease at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals.

Novel insights into the consequences of obesity: a phenotype-wide Mendelian randomization study
C He et al, EJHG January 1, 2022 (Posted: Jan 03, 2022 2PM)

Obesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 — Six Hospitals, United States, July–August 2021
V Wanga et al, MMWR, December 31, 2021 (Posted: Dec 31, 2021 7AM)

Pediatric COVID-19–related hospitalization rates increased when the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant became the predominant circulating strain. Among children and adolescents with SARS-CoV-2 infection admitted to six hospitals during July–August 2021, 77.9% were hospitalized for acute COVID-19. Among these patients, approximately one third aged <5 years had a viral coinfection (approximately two thirds of which were respiratory syncytial virus) and approximately two thirds of those aged 12–17 years had obesity; only 0.4% of age-eligible patients were fully vaccinated.

Obesity-Associated GNAS Mutations and the Melanocortin Pathway.
Mendes de Oliveira Edson et al. The New England journal of medicine 2021 10 (Posted: Oct 07, 2021 6AM)

We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays. Almost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth.

The genetics of obesity: from discovery to biology
RJF Loos et al, Nat Rev Genetics, September 23, 2021 (Posted: Sep 24, 2021 6AM)

Genome-wide association studies (GWAS) with increasing sample sizes and advances in sequencing technology are the main drivers behind a recent flurry of new discoveries. However, it is the post-GWAS, cross-disciplinary collaborations, which combine new omics technologies and analytical approaches, that have started to facilitate translation of genetic loci into meaningful biology and new avenues for treatment.

Impact of paternal education on epigenetic ageing in adolescence and mid-adulthood: a multi-cohort study in the USA and Mexico.
Joyce Brian T et al. International journal of epidemiology 2021 9 (Posted: Sep 19, 2021 10AM)

Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)—the discrepancy between chronological and epigenetic ages.We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. Our findings suggest that EAA captures epigenetic impacts of paternal education independently of personal SES later in life.

Antibody responses to BNT162b2 mRNA vaccine: infection-naive individuals with abdominal obesity warrant attention
AE Malavazoz et al, MEDRXIV, September 14, 2021 (Posted: Sep 15, 2021 8AM)

Obesity genes open new avenues of research - A large-scale genetic sequencing study reveals a potential new therapeutic target in obesity.
K O'Leary, Nature Medicine, July 29, 2021 (Posted: Jul 31, 2021 9AM)

Obesity accounts for a major burden of disease globally, and has a heritable component. However, previous efforts to define the genetics of obesity have failed to unearth rare variants associated with a large physiological effect; achieving this will require a large-scale sequencing-based approach.

Obesity, Ethnicity, and Covid-19 Mortality: A population-based cohort study of 12.6 Million Adults in England
T Yates et al, MEDRXIV, July 23, 2021 (Posted: Jul 24, 2021 8AM)

Obesity and ethnicity are well characterized risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population. This large population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations.

Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial
V Munacu et al, Nature Medicine, July 5, 2021 (Posted: Jul 06, 2021 8AM)

We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n?=?17), FMT-LF (n?=?17), HF (n?=?17) and LF (n?=?19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6?weeks.

Finding genes that control body weight
GSH Yeo et al, Science, July 2, 2021 (Posted: Jul 02, 2021 7AM)

The principles of discovery go beyond that of body weight control and obesity. The exome sequencing approach at scale increases our ability to reach deep into the rare allele frequency spectrum for functionally compromised alleles. It bypasses the twin headaches of GWAS: the identification of the causative gene and the determination of direction of causality.

Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
S Akbari et al, Science, July 2, 2021 (Posted: Jul 02, 2021 7AM)

The authors sequenced more than 600,000 exomes from the United Kingdom, the United States, and Mexico and identified 16 rare coding variants (see the Perspective by Yeo and O'Rahilly). Some of the alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele was found in Mexican populations at low frequency and was associated with lower BMI.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.
et al. JAMA surgery 2021 7 (Posted: Jul 01, 2021 7AM)

Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown

Mendelian randomization suggests a bidirectional, causal relationship between physical inactivity and obesity
GD Carrasquilla, BIORXIV, June 19, 2021 (Posted: Jun 19, 2021 7AM)

Physical inactivity is associated with excess weight gain in observational studies. However, some longitudinal studies indicate reverse causality where weight gain leads to physical inactivity. As observational studies suffer from reverse causality, it is challenging to assess the true causal directions. Here, we assess the bidirectional causality between physical inactivity and obesity by bidirectional Mendelian randomization analysis. We used results from genome-wide association studies for accelerometer-based physical activity and sedentary time in 91,105 individuals and for body mass index (BMI) in 806,834 individuals.

The effect of obesity-related traits on COVID-19 severe respiratory symptoms is mediated by socioeconomic status: a multivariable Mendelian randomization study
BC Mendoza et al, MEDRXIV, June 12, 2021 (Posted: Jun 13, 2021 7AM)

Causality Inference of Obesity and Cancer Risk by Mendelian Randomization Analysis: Are We There yet?
S Yao et al, JNCI, May 21, 2021 (Posted: May 23, 2021 8AM)

Central obesity, smoking habit and hypertension are associated with a blunted serological response to COVID-19 mRNA vaccine
M Watanabe et al, MERXIV, April 15, 2021 (Posted: Apr 16, 2021 7AM)

Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection - Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021
RR Galang et al, MEDRXIV, March 1, 2021 (Posted: Mar 02, 2021 8AM)

Among 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30-39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, pregestational diabetes mellitus or gestational diabetes. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions.

Revealing the role of the human blood plasma proteome in obesity using genetic drivers.
Zaghlool Shaza B et al. Nature communications 2021 2 (1) 1279 (Posted: Feb 26, 2021 8AM)

Many proteins have been linked to complex disorders and are also under substantial genetic control. Here, we investigate the associations between over 1000 blood circulating proteins and body mass index (BMI) in three studies including over 4600 participants. We show that BMI is associated with widespread changes in the plasma proteome. We observe 152 replicated protein associations with BMI.

Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study).
Brandkvist Maria et al. PLoS medicine 2020 Dec (12) e1003452 (Posted: Dec 16, 2020 8AM)

Could the interplay between genes and an obesogenic environment play a role in growing differences in obesity risk among individuals with varying genetic predisposition? Longitudinal data from 67,000 people reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. The results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors.

The Promise of Lifestyle Interventions in Individuals With Genetically Higher Risk for Obesity.
Hivert Marie-France et al. JAMA pediatrics 2020 Dec e205180 (Posted: Dec 15, 2020 8AM)

Efforts to identify genetic variants that truly recognize individuals who may respond more or less to lifestyle interventions targeting weight have been limited. One lesson is to remind patients, “you are not doomed by your genes.” Lifestyle interventions can work and maybe work even better in individuals with a genetically higher risk for obesity.

Obesity Genes and Weight Loss During Lifestyle Intervention in Children With Obesity.
Heitkamp Melanie et al. JAMA pediatrics 2020 Dec e205142 (Posted: Dec 15, 2020 8AM)

In this interventional genetic association study that included 1198 children with overweight or obesity, 5 of 56 obesity single-nucleotide variants were statistically significantly associated with changes in body weight, however, only to a minor degree. Environmental, social, and behavioral factors play a substantial role in obesity treatment strategies.

Obesity as a predictor for adverse outcomes among COVID-19 patients: A meta-analysis
P Das et al, MEDRXIV, November 30, 2020 (Posted: Nov 30, 2020 2PM)

Rising incidence of early-onset colorectal cancer - a call to action.
Akimoto Naohiko et al. Nature reviews. Clinical oncology 2020 Nov (Posted: Nov 24, 2020 8AM)

The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity.

Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study
N Aung et al, Front in Genetics, November 11, 2020 (Posted: Nov 12, 2020 8AM)

Using Mendelian randomization in the UK biobank, we identified causal associations between BMI, LDL cholesterol and susceptibility to COVID-19. In particular, individuals in higher genetic risk categories were predisposed to SARS-CoV-2 infection. These findings support the integration of BMI into the risk assessment of COVID-19 and allude to a potential role of lipid modification in the prevention and treatment.

Impact of body composition on COVID-19 susceptibility and severity: a two-sample multivariable Mendelian randomization study
D Freuer et al, MEDRXIV, October 24,2020 (Posted: Oct 25, 2020 10AM)

Using Mendelian randomization, we investigated the causal impact of body composition on the susceptibility and severity of COVID-19. Genetically predicted BMI was strongly associated with both, susceptibility (OR=1.31 per 1 SD increase) and hospitalization (OR=1.62 per 1 SD increase) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD.

Characteristics Associated With Racial/Ethnic Disparities in COVID-19 Outcomes in an Academic Health Care System
T Gu et al, JAMA Network Open, October 21, 2020 (Posted: Oct 22, 2020 11AM)

In this cohort study of 5698 patients tested for or diagnosed with COVID-19, high population density, type 2 diabetes, and kidney disease were associated with hospitalization, in addition to older age, male sex, and obesity. Adjusting for covariates, non-Hispanic Black patients were 1.72-fold more likely to be hospitalized than non-Hispanic White patients.

How obesity could create problems for a COVID vaccine- Researchers fear that vaccines might not be as effective in people who are obese, a population already highly vulnerable to COVID-19.
H Ledford, Nature News, October 20, 2020 (Posted: Oct 20, 2020 1PM)

Risk Factors for Hospitalization, Mechanical Ventilation, or Death Among 10 131 US Veterans With SARS-CoV-2 Infection
GN Ioannou et al, JAMA Network Open, September 23, 2020 (Posted: Sep 23, 2020 1PM)

In this national cohort of VA patients, most SARS-CoV-2 deaths were associated with older age, male sex, and comorbidity burden. Many factors previously reported to be associated with mortality in smaller studies were not confirmed, such as obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking.

Why obesity worsens COVID-19
M Wadman, Science, September 11, 2020 (Posted: Sep 11, 2020 8AM)

Since the pandemic began, dozens of studies have reported that many of the sickest COVID-19 patients have been people with obesity. In recent weeks, that link has come into sharper focus as large new population studies have cemented the association and demonstrated that even people who are merely overweight are at higher risk.

Regardless of Age, Obesity and Hypertension Increase Risks With COVID-19
MH Katz, JAMA Internal Medicine, September 9, 2020 (Posted: Sep 09, 2020 3PM)

Obesity and Hypertension in the Time of COVID-19
G Rodgers et al, JAMA September 9, 2020 (Posted: Sep 09, 2020 3PM)

The confluence of disturbing trends in obesity, hypertension, and COVID-19 within communities of color appears to reflect a complex interplay of contributing factors that are rooted in the social determinants of health and structural racism.

From genetics to bariatric surgery and soda taxes: Using all the tools to curb the rising tide of obesity
A Misra et al, PLOS Medicine, July 31, 2020 (Posted: Aug 05, 2020 8AM)

While environmental and policy interventions to tackle obesity are often discussed separately from metabolic and genetic risk factors, researchers have increasingly linked environmental and biological components of risk to help personalize and direct interventions. The influence of genetic risk for obesity on food choice behaviors is not well understood.

Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank
G Jiang et al, PLOS Medicine, July 28, 2020 (Posted: Jul 29, 2020 8AM)

We found that the polygenic risk score (PRS) derived from 123 known risk variants for T2D was associated with early age of diagnosis and rapid glycemic progression, with validation in the replication cohort of HKDB, whereas the PRS derived from 63 BMI-related variants was associated with BMI but not glycemic progression.

Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US
S Gupta et al, JAMA Internal Medicine, July 15,2020 (Posted: Jul 16, 2020 6AM)

In a cohort of 2215 adults with COVID-19 who were admitted to intensive care units at 65 sites, 784 (35.4%) died within 28 days, with wide variation among hospitals. Factors associated with death included older age, male sex, obesity, coronary artery disease, cancer, acute organ dysfunction, and admission to a hospital with fewer intensive care unit beds.

Cardiometabolic traits, sepsis and severe covid-19 with respiratory failure: a Mendelian randomization investigation
PJ Mark et al, MEDRXIV, June 20, 2020 (Posted: Jun 22, 2020 8AM)

This mendelian randomization study used the UK biobank to investigate the role of several traits with COVID-19 severity. The findings support a causal effect of elevated BMI and smoking on risk of sepsis and severe covid-19. Clinical and public health interventions targeting obesity and smoking are likely to reduce sepsis and covid-19 related morbidity,

Inflammasome genetics and complex diseases: a comprehensive review
FP Fernandes et al, EJHG June 5, 2020 (Posted: Jun 06, 2020 6AM)

Several genetic variants in inflammasome components have been associated with common pathologies in the general population, such as autoimmune disorders, cardiovascular diseases, obesity and associated metabolic syndrome, neurodegenerative diseases, and cancer.

Nearly All Patients Hospitalized With Covid-19 Had Chronic Health Issues, Study Finds- Only 6 percent of patients at one New York area health system had no chronic conditions. Hypertension, obesity and diabetes were common.
RC Rabin, NY Times, April 23, 2020 (Posted: Apr 24, 2020 8AM)

Contribution of macronutrients to obesity: implications for precision nutrition
Nat Rev Endrocrinology, March 31, 2020 (Posted: Apr 04, 2020 9AM)

the interactions of the genetic make-up and/or microbiota features of a person with specific macronutrient intakes or dietary pattern consumption help to explain individualized responses to macronutrients and food patterns, which might represent key factors for comprehensive precision nutrition recommendations.

Obesity Treatment Among Adolescents- A Review of Current Evidence and Future Directions
JMI Cardel et al, AMA Pediatrics, March 26, 2020 (Posted: Mar 29, 2020 8AM)

Provision of evidence-based treatment options that are tailored and appropriate for the adolescent population is paramount, yet complex. The multifactorial etiology of obesity along with the significant changes that occur during the adolescent period increasingly complicate the treatment approach for adolescent obesity.

New research directions on disparities in obesity and type 2 diabetes.
Thornton Pamela L et al. Annals of the New York Academy of Sciences 2020 Feb 1461(1) 5-24 (Posted: Feb 26, 2020 9AM)

Evidence from big data in obesity research: international case studies.
Wilkins Emma et al. International journal of obesity (2005) 2020 Jan (Posted: Feb 05, 2020 8AM)

The case studies demonstrated how big data could be used to augment traditional data to capture a broader range of variables in the obesity system. They also showed that big data can present improvements over traditional data in relation to size, coverage, temporality, and objectivity. However, the case studies also encountered limitations and biases.

Is Early-Life Antibiotic Exposure Associated With Obesity in Children?
Azad Meghan B et al. JAMA network open 2020 Jan (1) e1919694 (Posted: Jan 26, 2020 7AM)

Interest in the microbiome and its role in the developmental origins of obesity has increased substantially in the past decade, prompting multiple studies on early-life antibiotic exposures and childhood obesity. In addition to 20 previous studies on this topic, there are 2 new reports that may provide additional findings.

A healthy childhood environment helps to combat inherited susceptibility to obesity
A Huels et al, BioRXIV, January 14, 2020 (Posted: Jan 16, 2020 8AM)

Cohort study with measurements of diet, lifestyle factors and anthropometry. Polygenic risk scores captured the inherited susceptibility of obesity were calculated using summary statistics from independent genome-wide association studies of BMI. We observed significant interactions with demographic and lifestyle factors for BMI as well as waist circumference.

Polygenic Risk, Fitness, and Obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
VL Murthy et al, JAMA Cardiology, January 8, 2020 (Posted: Jan 09, 2020 8AM)

Comprehensive clinical risk profiles (incorporating BMI, its change over time, and behavioral factors), but not polygenic risk scores, offer substantial predictive ability for future BMI in the context of obesity prevention.

The current obesity “epidemic”: segregation of familial genetic risk in NHANES cohort supports a major role for large genetic effects
AB Jenkins et al. BIORXIV, November 2019 (Posted: Nov 18, 2019 9AM)

The continuing increase in many countries in adult body mass index (BMI kg/m2) and its dispersion is contributed to by interaction between genetic susceptibilities and an increasingly obesogenic environment. This population study suggests that large genetic effects interacting with OE provide a better quantitative explanation for current trends in BMI.

Causal relationships between obesity and the leading causes of death in women and men.
Censin Jenny C et al. PLoS genetics 2019 Oct (10) e1008405 (Posted: Nov 16, 2019 7AM)

Using mendelian randomization, obesity traits were found to be causally involved in the majority of the leading causes of death, and some obesity traits affect disease risk differently in men and women. This has potential implications for public health strategies and indicates that sex-specific preventative measures may be needed.

Hype or hope?
Nature Rev Microbiology, November 12, 2019 (Posted: Nov 14, 2019 8AM)

The microbiota is booming — the number of studies mentioning ‘microbiome’ or ‘microbiota’ in their title or abstract grew from 11 in 1980 to over 13,000 in 2018. Almost any human disease you can think of has proposed links with the microbiome: inflammatory bowel disease, cancer, diabetes, obesity, atherosclerosis, fatty liver disease, autism, Alzheimer disease..

Pancreatic Cancer: Patient Page
JAMA, October 2019 (Posted: Oct 13, 2019 1PM)

Conditions that increase risk of pancreatic cancer include smoking, chronic pancreatitis, obesity, long-standing diabetes, a strong family history of pancreatic cancer, and diets high in red and processed meats.

Wearable technology and lifestyle management: the fight against obesity and diabetes
The Lancet Digital Health, Vol 1, Iss 6, Pe 243, October 1, 2019 (Posted: Oct 11, 2019 0PM)

A Patient’s Guide to Endometrial Cancer-This cancer is on the rise. But early detection saves lives.
MO Shroeder, US News, October 4, 2019 (Posted: Oct 05, 2019 9AM)

Risk factors for this cancer include: obesity, diabetes, having close relatives like a parent or sibling who have endometrial cancer or colorectal cancer, and a genetic condition called Lynch syndrome. Having Lynch syndrome greatly increases a woman’s risk of developing endometrial cancer, and other cancers like colon and ovarian cancer

Adult Obesity Prevalence Maps
CDC, September 12, 2019 Brand (Posted: Sep 13, 2019 9AM)

Each year CDC releases the Adult Obesity Prevalence Maps for all 50 states, the District of Columbia, and US territories. The maps show self-reported adult obesity prevalence by race, ethnicity, and location. The data comes from the Behavioral Risk Factor Surveillance System.

Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index: an observational study of 335,046 UK Biobank participants
KE Mason et al, MedRXIV, August 2019 (Posted: Sep 04, 2019 5AM)

Artificial intelligence for medicine needs a Turing test. Obesity would be a good one
M Joyner, StatNews, August 28, 2019 (Posted: Aug 28, 2019 7AM)

If you read high-profile medical journals, the high-end popular press, and magazines like Science or Nature, it is clear that the medicalization of artificial intelligence, machine learning, and big data is in full swing. Speculation abounds about what these can do for medicine. It’s time to put them to the test.

Leveraging Omics Profiling to Advance the Treatment of Pediatric Obesity.
Koch Sarah et al. JAMA pediatrics 2019 Aug (Posted: Aug 27, 2019 7AM)

Circulating microbiota-derived metabolites: a "liquid biopsy?
Aragonès Gemma et al. International journal of obesity (2005) 2019 Aug (Posted: Aug 19, 2019 8AM)

The workout that excels at countering obesity genes
Nature, August 2, 2019 (Posted: Aug 08, 2019 8AM)

Even people whose genes make them prone to obesity can keep the disease in check by jogging, walking or climbing mountains, according to research on more than 18,000 residents of Taiwan. But swimming and cycling might not be so successful at mitigating that genetic risk.

Lessons Learned from the POUNDS Lost Study: Genetic, Metabolic, and Behavioral Factors Affecting Changes in Body Weight, Body Composition, and Cardiometabolic Risk
Bray GA et al, Current Obesity Reports, August 2019 (Posted: Aug 03, 2019 0PM)

Performing different kinds of physical exercise differentially attenuates the genetic effects on obesity measures: Evidence from 18,424 Taiwan Biobank participants.
Lin Wan-Yu et al. PLoS genetics 2019 Aug (8) e1008277 (Posted: Aug 02, 2019 8AM)

Development and validation of a prediction model for fat mass in children and adolescents: meta-analysis using individual participant data.
Hudda Mohammed T et al. BMJ (Clinical research ed.) 2019 07 l4293 (Posted: Jul 29, 2019 8AM)

The study developed and validated a prediction model for fat mass in children aged 4-15 years using routinely available risk factors of height, weight, and demographic information without the need for more complex forms of assessment.

Fecal Transplants May Hold Promise in Treating Obesity
Pagel AS, Medscape, July 23, 2019 (Posted: Jul 25, 2019 11AM)

Should obesity be recognised as a disease?
JPH Wilding et al, BMJ, July 17, 2019 (Posted: Jul 22, 2019 8AM)

Genetic and environmental factors contribute to the etiology of obesity and influence the underlying biology of weight regulation, the sites of fat storage, and the risk of complications. This point-counterpoint presents the pros and cons of recognizing obesity as a "diseases".

Genome-Wide Polygenic Score Quantifies Inherited Susceptibility to Obesity
Mass General Hospital, July 3, 2019 (Posted: Jul 10, 2019 9AM)

Destigmatising obesity by understanding the impact of genes
M Brandkvist, BMJ Opinion, July 3, 2019 (Posted: Jul 08, 2019 8AM)

The obese are often stigmatized for having unhealthy lifestyle choices. Acknowledging the importance of the obesogenic environment and its amplification of our genetic differences, can help destigmatise obesity. Perhaps it is time to shift our focus away from the individual and towards a healthier society.

Quantifying the impact of genes on body mass index during the obesity epidemic: longitudinal findings from the HUNT Study.
Brandkvist Maria et al. BMJ (Clinical research ed.) 2019 Jul l4067 (Posted: Jul 07, 2019 0PM)

This large cohort study provides evidence that genetically predisposed people are at greater risk for higher BMI and that genetic predisposition interacts with the obesogenic environment resulting in higher BMI, as observed between the mid-1980s and mid-2000s. Regardless, BMI has increased for both genetically predisposed and non-predisposed people, implying that the environment remains the main contributor.

A Scientific Overview of Smartphone Applications and Electronic Devices for Weight Management in Adults
SL Holzmann et al, MDPI, June 7, 2019 (Posted: Jun 13, 2019 2PM)

The association between maternal body mass index and child obesity: A systematic review and meta-analysis.
Heslehurst Nicola et al. PLoS medicine 2019 Jun (6) e1002817 (Posted: Jun 12, 2019 7AM)

Weight management telehealth intervention for overweight and obese rural cardiac rehabilitation participants: A randomised trial.
Barnason Susan et al. Journal of clinical nursing 2019 May 28(9-10) 1808-1818 (Posted: May 29, 2019 9AM)

Lifestyle Interventions for Weight Control Modified by Genetic Variation: A Review of the Evidence.
Tan Pui Yee et al. Public health genomics 2019 May 1-17 (Posted: May 27, 2019 5PM)

Predicting nationwide obesity from food sales using machine learning.
Dunstan Jocelyn et al. Health informatics journal 2019 May 1460458219845959 (Posted: May 22, 2019 8AM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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