ArticleBiological psychiatry2015
A genome-wide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity?
Article in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
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Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Molecular autism · 2017Pooled it
- Prevalence of Decreased Sound Tolerance (Hyperacusis) in Individuals With Autism Spectrum Disorder: A Meta-Analysis.Ear and hearingPooled it
- Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study.Translational psychiatry · 2019Trial
- Environmental Enrichment Therapy for Autism: Outcomes with Increased Access.Neural plasticity · 2016Trial
- Review
- Review
- Current Approaches in Computational Psychiatry for the Data-Driven Identification of Brain-Based Subtypes.Biological psychiatry · 2023Review
- Article
- Maternal-fetal genetic interactions, imprinting, and risk of placental abruption.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2022Article
- Genetic correlates of phenotypic heterogeneity in autism.Nature genetics · 2022Article
- Re-Examining Labels in Neurocognitive Research: Evidence from Bilingualism and Autism as Spectrum-Trait Cases.Brain sciences · 2022Review
- Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future.Genes, brain, and behavior · 2022Review
- Genomics, convergent neuroscience and progress in understanding autism spectrum disorder.Nature reviews. Neuroscience · 2022Review
- Identification of novel potential biomarkers in infantile hemangioma via weighted gene co-expression network analysis.BMC pediatrics · 2022Article
- Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders.Frontiers in psychiatry · 2022Article
- How rare and common risk variation jointly affect liability for autism spectrum disorder.Molecular autism · 2021Article
- Response to "A radical change in our autism research strategy is needed: Back to prototypes" by Mottron et al. (2021).Autism research : official journal of the International Society for Autism Research · 2021Article
- Genetic contributions to autism spectrum disorder.Psychological medicine · 2021Review
- Review
- Identifying Subgroups of Patients With Autism by Gene Expression Profiles Using Machine Learning Algorithms.Frontiers in psychiatry · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors.
Funding
Abstract
backgroundPhenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of subphenotyping of a well-characterized autism spectrum disorder (ASD) sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD.
methodsGenome-wide genotypic data of 2576 families from the Simons Simplex Collection were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study, as well as estimating heritability and evaluating allele scores for each phenotypic subgroup.
resultsAssociation analyses revealed no genome-wide significant association signal. Subphenotyping did not increase power substantially. Moreover, allele scores built from the most associated single nucleotide polymorphisms, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups.
conclusionsIn genome-wide association analysis of the Simons Simplex Collection sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of subphenotypes is not a productive path forward for discovering genetic risk variants in ASD.
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