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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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201 hot topic(s) found with the query "Autism"

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). "

Digital phenotyping could help detect autism.
Catherine Lord et al. Nat Med 2023 10 (Posted: Oct 07, 2023 8AM)

From the paper: " Researchers have developed a screening tool for autism that uses computer vision and machine learning to analyze autism-related behaviors — but greater reliability and robust validation will be needed if such tools are to be used in primary care settings."

Scientists discover how dozens of genes may contribute to autism
M Johnson, The Washington Post, October 5, 2023 (Posted: Oct 06, 2023 11AM)

From the article: "Using a host of high-tech tools to simulate brain development in a lab dish, researchers have discovered several dozen genes that interfere with crucial steps in the process and may lead to autism, a spectrum of disorders that affects about one in every 36 Americans, impairing their ability to communicate and interact with others. The results of a decade of work may one day pave the way for scientists to design treatments that allow these phases of brain development to proceed unimpaired. "

Early detection of autism using digital behavioral phenotyping
S Perochon et al, Nature Medicine, October 2, 2023 (Posted: Oct 02, 2023 11AM)

From the abstract: "Early detection of autism, a neurodevelopmental condition associated with challenges in social communication, ensures timely access to intervention. Autism screening questionnaires have been shown to have lower accuracy when used in real-world settings, such as primary care, as compared to research studies, particularly for children of color and girls. Here we report findings from a multiclinic, prospective study assessing the accuracy of an autism screening digital application (app) administered during a pediatric well-child visit to 475 (17–36 months old) children (269 boys and 206 girls). "

Underdiagnosis of autism in children with fragile X syndrome reveals need for better education, early screening
E Bluvas, Medical Xpress, August 2023 (Posted: Sep 01, 2023 0PM)

From the article: A recent study "conducted comprehensive, best-practice clinical autism diagnostic assessments in young males (ages 15-24) with fragile X syndrome (i.e., the most common single-gene cause of autism spectrum disorder and other intellectual disabilities). The study found that, although 75 percent of participants met criteria for autism through the research protocol, only 31 percent had been identified as having autism in the community."

Study proposes use of artificial intelligence to diagnose autism spectrum disorder
R Muniz, Medical XPress, August 2023 (Posted: Aug 18, 2023 11AM)

Much recent research proposes methods for diagnosing ASD based on machine learning but uses a single statistical parameter, ignoring brain network organization, which is the innovation featured by this study, the article notes. The analysis of fMRI data highlighted changes in certain brain regions associated with cognitive, emotional, learning and memory processes.

Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies
C Lowther et al, AJHG, August 17, 2023 (Posted: Aug 18, 2023 8AM)

Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.

Evaluation of Birth Weight and Neurodevelopmental Conditions Among Monozygotic and Dizygotic Twins.
Johan Isaksson et al. JAMA Netw Open 2023 6 (6) e2321165 (Posted: Jul 01, 2023 9AM)

After adjustment for genetic factors, is birth weight associated with neurodevelopmental conditions? In this case-control study of 393 twins in Sweden, the twin with a lower birth weight in monozygotic twin pairs, but not dizygotic pairs, had more autism and attention-deficit/hyperactivity disorder (ADHD) symptoms, lower IQ ratings, and higher odds of having a diagnosis of autism and ADHD compared with their co-twin. These findings suggest that birth weight contributes to neurodevelopmental conditions when adjusting for genetic factors.

Phenotypic effects of genetic variants associated with autism.
Thomas Rolland et al. Nat Med 2023 6 (Posted: Jun 28, 2023 10AM)

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants.

Contemplating syndromic autism
JA Vortsmann et al, Genetics in Medicine, June 15, 2023 (Posted: Jun 16, 2023 1PM)

Genetic factors contribute to the etiology of autism spectrum disorder (ASD), a group of neurodevelopmental conditions with an estimated population prevalence of 2.3%. Further elucidation of the genetic architecture underlying ASD continues. Against this backdrop, we review history and current use of the concept “syndromic autism”, which refers to both genetic etiology and phenotypic co-comorbidity. We question whether this term is still helpful, both in clinical and in research contexts.

Prosodic signatures of ASD severity and developmental delay in preschoolers.
Michel Godel et al. NPJ Digit Med 2023 5 (1) 99 (Posted: May 30, 2023 6AM)

Atypical prosody in speech production is a core feature of Autism Spectrum Disorder (ASD) that can impact everyday life communication. Because the ability to modulate prosody develops around the age of speech acquisition, it might be affected by ASD symptoms and developmental delays that emerge at the same period. Here, we investigated the existence of a prosodic signature of developmental level and ASD symptom severity in a sample of 74 autistic preschoolers.

How one man's rare Alzheimer’s mutation delayed the onset of disease Genetic resilience found in a person predisposed to early-onset dementia could potentially lead to new treatments.
S Reardon, Nature, May 16, 2023 (Posted: May 16, 2023 9AM)

The researchers found that the man had a mutation in a gene coding for a protein called reelin, which is associated with brain disorders including schizophrenia and autism. Little is known about reelin’s role in Alzheimer’s. The study challenges the theory that Alzheimer’s disease is primarily driven by amyloid plaques, which are the targets of several drugs recently approved by the US Food and Drug Administration. The drugs effectively remove amyloid from the brain, but lead to only a moderate improvement in rates of cognitive decline.

Interactions between the lipidome and genetic and environmental factors in autism.
Chloe X Yap et al. Nat Med (4) 936-949 (Posted: Apr 20, 2023 9AM)

Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n?=?8), sleep disturbances (n?=?20) and cognitive function (n?=?8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster.

What is Autism Spectrum Disorder?
CDC, 2023 Brand (Posted: Mar 24, 2023 7AM)

Autism spectrum disorder (ASD) is a developmental disability caused by differences in the brain. Some people with ASD have a known difference, such as a genetic condition. Other causes are not yet known. Scientists believe there are multiple causes of ASD that act together to change the most common ways people develop.

All Patients With a Cerebral Palsy Diagnosis Merit Genomic Sequencing.
Clare van Eyk et al. JAMA pediatrics 2023 3 (Posted: Mar 07, 2023 6PM)

A recent meta-analysis provides strong data to justify the cost of genomic sequencing. The diagnostic yield for cerebral palsy is similar to other neurodevelopmental disorders, such as developmental delay, intellectual disability, and autism spectrum disorder, where genomic sequencing has been largely accepted as a first-tier test. Including genomic sequencing as a routine diagnostic test can circumvent lengthy, costly, and sometimes invasive clinical investigations to determine etiology where a clinical diagnosis of cerebral palsy has been made.

Cohort-guided insights into gene-environment interactions in autism spectrum disorders.
W Ian Lipkin et al. Nature reviews. Neurology 2023 1 1-8 (Posted: Feb 02, 2023 6AM)

Prospective birth cohorts offer unprecedented opportunities to investigate the pathogenesis of complex disorders such as autism, in which gene–environment interactions must be appreciated in a temporal context. This Perspective article considers the history of autism research, including missteps that reflected an incomplete understanding of the epidemiology of autistic spectrum disorders, the effects of advocacy and philanthropy on the trajectory of scientific inquiry, and the current and future roles of prospective birth cohort research.

Exploring Autistic adults' perspectives on genetic testing for autism.
Byres Loryn et al. Genetics in medicine : official journal of the American College of Medical Genetics 2023 1 100021 (Posted: Jan 22, 2023 8AM)

In total 461 respondents completed the survey: while 27% would have wanted genetic testing during childhood, 74% felt that it should only be offered if the Autistic individual is able to consent and 49% felt that genetic testing for autism should not be done at all. Additional work is required to bridge the divide between the Autistic community and health care providers and families to identify if and when genetic testing should be offered.

Ribosomal DNA Abundance in the Patient’s Genome as a Feasible Marker in Differential Diagnostics of Autism and Childhood-Onset Schizophrenia
ES Ershova et al, J Per Med, October 31, 2022 (Posted: Oct 31, 2022 9AM)

Rare and common autism risk variants converge across 16p.
Won Hyejung et al. Nature genetics 2022 10 (Posted: Oct 28, 2022 9AM)

Genetic risk factors for autism include both rare and common variants. A study shows that rare copy number variants and common variants across 16p that contribute to autism risk functionally converge to downregulate the expression of a large group of neuronally expressed genes in the 16p subtelomeric region.

Metabolomic Signatures of Autism Spectrum Disorder
D Brister et al, J Per Med, October 17, 2022 (Posted: Oct 17, 2022 7AM)

Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups.
Mattheisen Manuel et al. Nature genetics 2022 9 (Posted: Sep 28, 2022 7AM)

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits.

Diverse mutations in autism-related genes and their expression in the developing brain
Nature Genetics, August 18, 2022 (Posted: Aug 18, 2022 1PM)

Across >150,000 individuals, we identified hundreds of genes associated with autism spectrum disorder (ASD) and atypical neurodevelopment. Most ASD-related genes were also associated with developmental delay. However, increased mutation rates in ASD and shared genetic risk with schizophrenia was observed for some genes, many of which are enriched in developing neurons.

Rare coding variation provides insight into the genetic architecture and phenotypic context of autism
JM Fu et al, Nature Genetics, August 18, 2022 (Posted: Aug 18, 2022 1PM)

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR)?=?0.001 (185 at FDR?=?0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk.

Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes
X Zhou et al, Nature Genetics, August 18, 2022 (Posted: Aug 18, 2022 1PM)

To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P?<?2.5?×?10-6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect

Stratifying the autistic phenotype using electrophysiological indices of social perception
L Mason et al, Sci Trans Med, August 17, 2022 (Posted: Aug 17, 2022 2PM)

We evaluated the use of the speed of early-stage face processing (N170 latency) for patient stratification and prognosis in subjects with ASD and age-matched healthy individuals. N170 latency was slower in individuals with ASD and correlated with response to faces measured with fMRI and with polygenic risk score. Among subjects with ASD, the N170 values stratified patients according to socialization prognosis and improved power in a simulated clinical trial. The results suggest that including N170 evaluation in patient stratification might help the design and development of patient-specific therapies for ASD.

Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder.
Rajagopal Veera M et al. Nature genetics 2022 8 (Posted: Aug 05, 2022 8AM)

We evaluated genetic differences among childhood (n?=?14,878), persistent (n?=?1,473) and late-diagnosed (n?=?6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD.

Developmental Variability in Autism Across 17 000 Autistic Individuals and 4000 Siblings Without an Autism Diagnosis Comparisons by Cohort, Intellectual Disability, Genetic Etiology, and Age at Diagnosis
SS Kuo et al, JAMA Pediatrics, July 18, 2022 (Posted: Jul 18, 2022 1PM)

Using retrospective, parent-report data from 17?098 autistic individuals in this cross-sectional study we found substantial variability in average developmental milestone acquisition. Average delays increased with co-occurring intellectual disability, presence of a genetic variant associated with neurodevelopmental disorders, earlier autism diagnosis, and participation in older autism cohorts, and average delays also were larger for later milestones (eg, phrase speech, bowel control) than earlier milestones (eg, smiling, sitting).

The performance of artificial intelligence-driven technologies in diagnosing mental disorders: an umbrella review
A Abd-Alrazak et al, NPJ Digital Medicine, July 7, 2022 (Posted: Jul 08, 2022 7AM)

We included 15 systematic reviews of 852 citations identified. The included reviews assessed the performance of AI models in diagnosing Alzheimer’s disease (n?=?7), mild cognitive impairment (n?=?6), schizophrenia (n?=?3), bipolar disease (n?=?2), autism spectrum disorder (n?=?1), obsessive-compulsive disorder (n?=?1), post-traumatic stress disorder (n?=?1), and psychotic disorders (n?=?1). The performance of the AI models in diagnosing these mental disorders ranged between 21% and 100%. AI technologies offer great promise in diagnosing mental health disorders. The reported performance metrics paint a vivid picture of a bright future for AI in this field.

Contrastive machine learning reveals the structure of neuroanatomical variation within autism.
Aglinskas Aidas et al. Science (New York, N.Y.) 2022 6 (6597) 1070-1074 (Posted: Jun 04, 2022 7AM)

Autism spectrum disorder (ASD) is highly heterogeneous. Identifying systematic individual differences in neuroanatomy could inform diagnosis and personalized interventions. The challenge is that these differences are entangled with variation because of other causes: individual differences unrelated to ASD and measurement artifacts. We used contrastive deep learning to disentangle ASD-specific neuroanatomical variation from variation shared with typical control participants. ASD-specific variation correlated with individual differences in symptoms. The structure of this ASD-specific variation also addresses a long-standing debate about the nature of ASD: At least in terms of neuroanatomy, individuals do not cluster into distinct subtypes; instead, they are organized along continuous dimensions that affect distinct sets of regions.

A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex.
Antaki Danny et al. Nature genetics 2022 6 (Posted: Jun 03, 2022 10AM)

Genetic correlates of phenotypic heterogeneity in autism.
Warrier Varun et al. Nature genetics 2022 6 (Posted: Jun 03, 2022 10AM)

We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males.

Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels
ER Riggs et al, Genetics in Medicine, May 26, 2022 (Posted: May 27, 2022 6AM)

Using the Clinical Genome Resource gene–disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. As of September 2021, 156 gene–disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants.

Evaluation of an artificial intelligence-based medical device for diagnosis of autism spectrum disorder
JK Megerian et al, NPJ DIgital Medicine, May 5, 2022 (Posted: May 05, 2022 6AM)

This double-blinded, multi-site, prospective, active comparator cohort study tested the accuracy of an artificial intelligence-based Software as a Medical Device designed to aid primary care healthcare providers (HCPs) in diagnosing ASD. The Device combines behavioral features from three distinct inputs (a caregiver questionnaire, analysis of two short home videos, and an HCP questionnaire) in a gradient boosted decision tree machine learning algorithm to produce either an ASD positive, ASD negative, or indeterminate output. This study compared Device outputs to diagnostic agreement by two or more independent specialists in a cohort of 18–72-month-olds with developmental delay concerns.

Exploring polygenic contributors to subgroups of comorbid conditions in autism spectrum disorder
L Klein et al, Scientific Reports, March 1, 2022 (Posted: Mar 02, 2022 7AM)

Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial
AS Campbell et al, Nature Medicine, February 14, 2022 (Posted: Feb 15, 2022 7AM)

A pilot human study was designed and completed to evaluate the safety of AB-2004 in an open-label, single-cohort, multiple-ascending-dose clinical trial that enrolled 30 adolescents with ASD and GI symptoms in New Zealand and Australia. AB-2004 was shown to have good safety and tolerability across all dose levels, and no drug-related serious adverse events were identified. Significant reductions in specific urinary and plasma levels of gut bacterial metabolites were observed between baseline and end of AB-2004 treatment, demonstrating likely target engagement. Furthermore, we observed improvements in multiple exploratory behavioral endpoints, most significantly in post hoc analysis of anxiety and irritability, as well as GI health, after 8 weeks of treatment.

Understanding microbiome alterations in autism
K O'Leary, Nature Medicine, January 2022 (Posted: Jan 27, 2022 10AM)

Studies have suggested that alterations in the gut microbiome may be involved in the development of autism spectrum disorder (ASD), but data are inconsistent and a definitive causal role has not been established. A new study found negligible evidence for a direct association between the gut microbiome and diagnosis of autism, or autism-associated behaviors. In contrast, they found that microbiome composition was strongly associated with diet, age and stool consistency. Many people with ASD have restricted diets due to ASD-associated food selectivity — therefore, a lack of dietary diversity may in turn limit microbial diversity and stool consistency.

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health
J Johannessen et al, EJHG, November 15, 2021 (Posted: Nov 15, 2021 6AM)

We investigated attitudes towards sharing information about genetic risk of ASD and knowledge about future health among parent members of the Norwegian Autism Association (N?=?1455) using a questionnaire, and the relationships with parent and child characteristics, such as age, gender and ASD severity. Most preferred autonomy in deciding whom to inform about genetic risk of ASD (74.4%) and a minority supported extensive intra-familial disclosure of the genetic risk (41.1%). The majority agreed that it is an obligation to know as much as possible relevant for future health (58.0%) and only 51.7% agreed to a principle of a ‘right not to know’.

High-profile autism genetics project paused amid backlash Study aimed at collecting DNA from 10,000 people with autism and their families has drawn criticism for failing to consult the autism community.
K Sandarson, Nature, September 27, 2021 (Posted: Sep 28, 2021 6AM)

Recent ultra-rare inherited variants implicate new autism candidate risk genes
AB Wilfert et al, Nature Genetics, July 26, 2021 (Posted: Jul 26, 2021 11AM)

Autism is a highly heritable complex disorder in which de novo mutation (DNM) variation contributes significantly to risk. Using whole-genome sequencing data from 3,474 families, we investigate another source of large-effect risk variation, ultra-rare variants. We report and replicate a transmission disequilibrium of private, likely gene-disruptive (LGD) variants in probands but find that 95% of this burden resides outside of known DNM-enriched genes. This variant class more strongly affects multiplex family probands and supports a multi-hit model for autism.

AI-Based Software Accurately Identifies Autism
T Bosworth, Medscape, June 2021 (Posted: Jun 29, 2021 6AM)

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions. The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire.

Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)
L Shao et al, Genetics in Medicine, June 15, 2021 (Posted: Jun 16, 2021 8AM)

Chromosomal microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism array, are widely applied in the diagnostic evaluation for both constitutional and neoplastic disorders. In a constitutional setting, this technology is accepted as the first-tier test for the evaluation of chromosomal imbalances associated with intellectual disability, autism, and/or multiple congenital anomalies.

Association of Polygenic Liability for Autism With Face-Sensitive Cortical Responses From Infancy.
Gui Anna et al. JAMA pediatrics 2021 6 (Posted: Jun 09, 2021 7AM)

The N170 precursor (N290) to faces vs nonfaces is also altered prior to symptom emergence in infants subsequently diagnosed with autism.3 These early differences in brain processing represent a plausible developmental mechanism linking genetic liability and behavioral autism symptoms. We investigated whether N290 latency to faces vs nonfaces is associated with autism polygenic scores and cross-disorder polygenic scores in infants with and without a family history of autism.

A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex
D Antaki et al, MEDRXIV, April 4, 2021 (Posted: Apr 05, 2021 8AM)

New ASD prevalence numbers show gaps are closing, but more work is needed
CDC, April, 2021 Brand (Posted: Apr 03, 2021 7AM)

Recent findings from the ADDM Network show that an estimated 1 in 54 8-year-old children were identified with ASD in 2016, based on tracking in 11 communities across the United States. For the first time, ADDM Network data found no overall difference in the number of black children identified with ASD compared to white children.

Understanding Pregnancy Loss, Infertility, Birth Defects and the MTHFR gene: What Everyone Should Know
J Gunter, the Vajenda, March 27, 2021 (Posted: Mar 29, 2021 6AM)

Many people have erroneously linked MTHFR polymorphisms with a myriad of medical conditions. In the world of reproductive medicine, it is blamed for a host of things, such as infertility, miscarriages, stillbirths, failure of in vitro fertilization (IVF), preecplampsia (a serious medical condition during pregnancy), and having a child with autism, Down syndrome, birth defects that impact the heart (congenital heart disease), and neural tube defects.

Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
FM Granero et al, Genetics in Medicine February 25, 2021 (Posted: Mar 26, 2021 8AM)

412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and other NDDs.Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no additional cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH).

Autism Spectrum Disorder, Family Health History, and Genetics
CDC, March 2021 Brand (Posted: Mar 25, 2021 8AM)

If someone in your family has autism spectrum disorder (ASD), you may be more likely to have a child with ASD. ASD can look very different from person to person, so taking a careful family health history can be important for early diagnosis. Early screening and diagnosis of ASD can ensure that children receive the services they need for better outcomes.

Genetic contributions to autism spectrum disorder.
Havdahl A et al. Psychological medicine 2021 1-14 (Posted: Mar 02, 2021 9AM)

This review summarizes recent developments in human genetics research in autism, complemented by epigenetic and transcriptomic findings. The clinical heterogeneity of autism is mirrored by a complex genetic architecture involving several types of common and rare variants, ranging from point mutations to large copy number variants.

Linking newly occurring mutations to autism
NDG Burgess, Nature Rev Genetics, February 4, 2021 (Posted: Feb 06, 2021 7AM)

Three new studies identify different types of de novo and somatic mutations associated with autism spectrum disorder (ASD), with potential insights into underlying molecular mechanisms.

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift
C Panisi et al, JPM, January 2021 (Posted: Jan 26, 2021 8AM)

The epidemiological and clinical findings in autism spectrum disorder cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole.

Repeat DNA expands our understanding of autism spectrum disorder
AJ Hannan, Nature News, January 13, 2021 (Posted: Jan 14, 2021 8AM)

A link has been found between repetitive stretches of DNA called tandem repeats and autism spectrum disorder. The discovery might inform approaches to studying tandem repeats in a wide range of other human disorders.

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia
CA Moreau et al, Nature Comms, October 19, 2020 (Posted: Oct 20, 2020 7AM)

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls.

The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder
D Li et al, NPJ Genomic Medicine, October 12, 2020 (Posted: Oct 14, 2020 8AM)

Social skills group training (SSGT) is a frequently used behavioral intervention in autism spectrum disorder (ASD), but the effects are moderate and heterogeneous. Here, we analyzed the effect of polygenic risk score (PRS) and common variants in gene sets on the intervention outcome.

Fats in the blood linked to autism- Precision medicine offers insight into a particular form of the disorder.
Nature, August 13, 2020 (Posted: Aug 19, 2020 8AM)

By mining medical records and genome sequences, scientists have identified a form of autism that is characterized by unusual levels of fat molecules in the blood.

A multidimensional precision medicine approach identifies an autism subtype characterized by dyslipidemia
Y Luo et al, Nature Medicine, August 10, 2020 (Posted: Aug 11, 2020 7AM)

By combining healthcare claims, electronic health records, familial whole-exome sequences and neurodevelopmental gene expression patterns, we identified a subgroup of patients with dyslipidemia-associated autism.

Genome-wide detection of tandem DNA repeats that are expanded in autism
B Trost et al, Nature, July 27, 2020 (Posted: Jul 28, 2020 9AM)

Rare tandem repeat expansions had a prevalence of 23.3% in autism-affected children versus 20.7% in unaffected children, suggesting a collective contribution to autism risk of 2.6%. They included novel autism-linked tandem repeat expansions in DMPK and FXN, known for neuromuscular conditions, and in novel loci such as FGF14 and CACNB1.

Insufficient Evidence for “Autism-Specific” Genes
SM Myers et al, AJHG, May 7, 2020 (Posted: May 08, 2020 9AM)

Despite the evidence that deleterious variants in the same genes are implicated across multiple disorders, the recent literature reflects considerable interest in identifying genes that, when mutated, confer risk that is largely specific for ASD.

A framework for an evidence-based gene list relevant to autism spectrum disorder.
Schaaf Christian P et al. Nature reviews. Genetics 2020 Apr (Posted: Apr 23, 2020 8AM)

In clinical practice, providers need to decide which genes to test in individuals with ASD phenotypes, which requires an understanding of the level of evidence for individual genes that supports an association with ASD. Consensus is currently lacking about which NDD genes have sufficient evidence to support a relationship to ASD.

Identification of newborns at risk for autism using electronic medical records and machine learning.
Rahman Rayees et al. European psychiatry : the journal of the Association of European Psychiatrists 2020 Feb 63(1) e22 (Posted: Mar 04, 2020 9AM)

We conclude that machine learning algorithms combined with electronic medical records capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.

Towards the automatic detection of social biomarkers in autism spectrum disorder: introducing the simulated interaction task (SIT)
H Drimalla et al, NPJ Digital Medicine, February 27, 2020 (Posted: Feb 29, 2020 9AM)

Social interaction deficits are evident in many psychiatric conditions and specifically in autism spectrum disorder (ASD), but hard to assess objectively. We present a digital tool to automatically quantify biomarkers of social interaction deficits: the simulated interaction task (SIT).

Towards developing a practical artificial intelligence tool for diagnosing and evaluating autism spectrum disorder: A study using multicenter ABIDE II datasets.
Lu Long et al. JMIR medical informatics 2020 Feb (Posted: Feb 19, 2020 9AM)

Recent ultra-rare inherited mutations identify novel autism candidate risk genes
AB Wilfert et al, BIORXIV preprints, February 11, 2020 (Posted: Feb 12, 2020 8AM)

Using whole-genome sequencing data from 3,474 families, we investigate another source of large-effect risk variation, ultra-rare mutations. We report and replicate a transmission disequilibrium of private likely-gene disruptive (LGD) mutations in probands but find that 95% of this burden resides outside of known DNM-enriched genes.

Largest-Ever Genetic Study of Autism Yields New Insights
NIH Director Blog, February 2020 Brand (Posted: Feb 09, 2020 9AM)

A study of >35,000 people from around the world, the international Autism Sequencing Consortium identified variants in 102 genes associated with increased risk of developing ASD, up from 65 identified previously. Of the 102 genes, 60 had not been previously linked to ASD.

Study of Children with One vs. Two or More Siblings with Autism Spectrum Disorder: Expected and Unexpected Similarities and Differences
RF Green et al, CDC Blog Post, February 4, 2020 Brand (Posted: Feb 05, 2020 9AM)

Children with two or more siblings with autism spectrum disorder (ASD) were more than twice as likely to be classified as having ASD at age 3 than children with only one sibling with ASD. By finding these children early, interventions and therapies can begin sooner.

Autism heritability: It probably does not mean what you think it means
B Lee, Spectrum, January 7, 2020 (Posted: Jan 08, 2020 8AM)

Several studies on autism heritability published in the past few years have drawn considerable attention. Those published from 2011 to 2014 estimated heritability to be in the 35 to 50 percent range, but studies published since 2017 have put the number at 64 to 85 percent. What do these estimates actually mean?

Severity of autism symptoms varies greatly among identical twins
NIH News Release, December 27, 2019 Brand (Posted: Dec 27, 2019 5PM)

Identical twins with autism spectrum disorder (ASD) often experience large differences in symptom severity even though they share the same DNA. The findings suggest that identifying the causes of this variability may inform the treatment of ASD-related symptoms.

Autism risk in offspring can be assessed through quantification of male sperm mosaicism
MW Breus et al, Nature Medicine, December 23, 2019 (Posted: Dec 23, 2019 3PM)

We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father’s sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations.

Paternal sperm DNA mosaicism and recurrence risk of autism in families
Nature Medicine, December 23, 2019 (Posted: Dec 23, 2019 3PM)

Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.
D'Abate L et al. Nature communications 2019 Dec (1) 5519 (Posted: Dec 06, 2019 8AM)

The study describes clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically.

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..

A large data resource of genomic copy number variation across neurodevelopmental disorders
Mehdi Zarrei, et al. Genomic Medcine, October 7, 2019 (Posted: Oct 10, 2019 8AM)

Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. The study found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects.

Imaging the Whole Genome in Diagnosing Neurologic Disorders.
Mendelsohn Bryce A et al. JAMA neurology 2019 Oct (Posted: Oct 08, 2019 8AM)

Developmental Trajectories of Infants With Multiplex Family Risk for Autism: A Baby Siblings Research Consortium Study.
McDonald Nicole M et al. JAMA neurology 2019 Oct (Posted: Oct 08, 2019 8AM)

Infants with a multiplex family history of ASD should be monitored early and often and referred for early intervention at the first sign of concern. Direct examination of genetic contributions to neurodevelopmental phenotypes in infants with familial risk for ASD is needed.

A comparison of machine learning algorithms for the surveillance of autism spectrum disorder.
Lee Scott H et al. PloS one 2019 14(9) e0222907 (Posted: Oct 02, 2019 8AM)

CDC coordinates a labor-intensive process to measure the prevalence of autism spectrum disorder (ASD) among children in the United States. Random forests methods have shown promise in speeding up this process, but they lag behind human classification accuracy by 5%. We explore whether recently available document classification algorithms can close this gap.

Genetic Testing Experiences Among Parents of Children with Autism Spectrum Disorder in the United States.
Zhao Shixi et al. Journal of autism and developmental disorders 2019 Sep (Posted: Sep 25, 2019 9AM)

This study examined the experiences of Autism Spectrum Disorder (ASD) genetic testing among parents of children with ASD. A nationwide sample of 552 parents of children with ASD completed an online survey. Nearly one-quarter (22.5%) of the parents reported that their affected children had undergone ASD genetic testing.

Cross-disorder GWAS meta-analysis for Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive Compulsive Disorder, and Tourette Syndrome
Z Yang et al, BioRXIV, September 16, 2019 (Posted: Sep 17, 2019 7AM)

Getting to the Cores of Autism.
Iakoucheva Lilia M et al. Cell 2019 Sep (6) 1287-1298 (Posted: Sep 08, 2019 2PM)

The genetic architecture of autism spectrum disorder (ASD) is itself a diverse allelic spectrum that consists of rare de novo or inherited variants in hundreds of genes and common polygenic risk at thousands of loci. ASD susceptibility genes are interconnected in transcriptional and protein networks, and many function as genetic regulators of neurodevelopment.

Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
P Feliciano et al, NPJ Genomic Medicine, August23, 2019 (Posted: Aug 23, 2019 11AM)

What to Tell a Parent Who Worries a Young Child Has Autism.
Estes Annette et al. JAMA psychiatry 2019 Aug (Posted: Aug 12, 2019 8AM)

If a child is diagnosed with ASD, medical evaluation can determine whether co-occurring conditions, such as sensory motor difficulties, hearing problems, gastrointestinal symptoms, or seizures, are present. Genetic screening may identify known genetic syndromes that are associated with autism (eg, fragile X syndrome.

Phase 3 diagnostic evaluation of a smart tablet serious game to identify autism in 760 children 3-5 years old in Sweden and the United Kingdom.
Millar Lindsay et al. BMJ open 2019 Jul 9(7) e026226 (Posted: Jul 24, 2019 10AM)

The Architecture of Autism Spectrum Disorder Risk: What Do We Know, and Where Do We Go From Here?
Jutla Amandeep et al. JAMA psychiatry 2019 Jul (Posted: Jul 18, 2019 8AM)

Decades of research have implicated both genetic and environmental risk factors for autism spectrum disorder (ASD). However, only in recent years have population-based studies been able to place risk in a broader context, allowing the relative influence of these factors on ASD liability to be better estimated.

Recessive gene disruptions in autism spectrum disorder
RN Doan et al, Nature Genetics, June 17, 2019 (Posted: Jun 18, 2019 8AM)

Needs assessment in genetic testing education: A survey of parents of children with autism spectrum disorder in the united states.
Zhao Shixi et al. Autism research : official journal of the International Society for Autism Research 2019 Jun (Posted: Jun 12, 2019 8AM)

More evidence that autism is linked to gut bacteria
The Economist, May 30, 2019 (Posted: Jun 04, 2019 8AM)

Clinical and genetic analysis of children with a dual diagnosis of Tourette syndrome and autism spectrum disorder.
Carias Karin Vanessa et al. Journal of psychiatric research 2019 Apr 145-153 (Posted: Jun 03, 2019 10AM)

“Noncoding” Mutations May Play Unexpected Key Role in Autism
J Wright, Scientific American, June 2, 2019 (Posted: Jun 03, 2019 8AM)

Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk
J Zhou et al, Nature Genetics, May 27, 2019 (Posted: May 27, 2019 5PM)

New Data on Autism Spectrum Disorder in 4-Year-Old Children
CDC, April 2019 Brand (Posted: Apr 29, 2019 1PM)

Autism Spectrum Disorder
CDC, 2019 Brand (Posted: Apr 02, 2019 9AM)

Autism Spectrum Disorders and ADHD: Overlapping Phenomenology, Diagnostic Issues, and Treatment Considerations.
Antshel Kevin M et al. Current psychiatry reports 2019 Mar (5) 34 (Posted: Apr 02, 2019 9AM)

Nature versus nurture in autism
RM Jones, Science Trans Med, March 2019 (Posted: Mar 08, 2019 1PM)

Identification of common genetic risk variants for autism spectrum disorder
J Grove et al, Nature Genetics, February 25, 2019 (Posted: Feb 25, 2019 11AM)

Characterization of Intellectual disability and Autism comorbidity through gene panel sequencing
MC Aspromonte et al, BioRXIV, February 10, 2019 (Posted: Feb 13, 2019 9AM)

Potential for Digital Behavioral Measurement Tools to Transform the Detection and Diagnosis of Autism Spectrum Disorder
G Dawson et al, JAMA Pediatrics, February 4, 2019 (Posted: Feb 04, 2019 5PM)

Why genetic tests matter for autistic people
J Wright, Spectrum, January 2019 (Posted: Jan 31, 2019 10AM)

Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder.
Hegarty John P et al. Molecular psychiatry 2019 Jan (Posted: Jan 22, 2019 9AM)

Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder
M Miller et al, JAMA Pediatrics, December 10, 2018 (Posted: Dec 10, 2018 11AM)

Gut bacteria may offer a treatment for autism-A common probiotic holds the key
Economist, December 6, 2018 (Posted: Dec 10, 2018 9AM)

Calculating the Effects of Autism Risk Gene Variants on Dysfunction of Biological Processes Identifies Clinically-Useful Information
OJ Veatch et al, BIORXIV, October 22, 2018 (Posted: Oct 26, 2018 11AM)

Heterogeneity in clinical sequencing tests marketed for autism spectrum disorders
Ny Hoang et al, npj Genomic Medicine, Sepetmber 19, 2018 (Posted: Sep 19, 2018 1PM)

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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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