Journal
MOLECULAR AUTISM
Volume 3, Issue -, Pages -Publisher
BMC
DOI: 10.1186/2040-2392-3-9
Keywords
Narrow-sense heritability; Multiplex; Simplex; Quantitative genetics
Categories
Funding
- Simons Foundation [MH057881]
- National Institutes of Health [HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH57881, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261, HHSN268200782096C, HHSN268201100011I]
- Canadian Institutes for Health Research (CIHR)
- Assistance Publique - Hopitaux de Paris, France
- Autism Speaks UK
- Canada Foundation for Innovation/Ontario Innovation Trust [Po 255/17-4]
- Deutsche Forschungsgemeinschaft, Germany
- EC Sixth FP AUTISM MOLGEN
- Fundacao Calouste Gulbenkian, Portugal
- Fondation de France
- Fondation FondaMental, France
- Fondation Orange, France
- Fondation pour la Recherche Medicale, France
- Fundacao para a Ciencia e Tecnologia, Portugal
- Hospital for Sick Children Foundation and University of Toronto, Canada
- INSERM, France
- Institut Pasteur, France
- Italian Ministry of Health
- John P Hussman Foundation, USA
- McLaughlin Centre, Canada
- Netherlands Organization for Scientific Research [TMF/DA/5801]
- Royal Netherlands Academy of Arts and Sciences
- Ontario Ministry of Research and Innovation, Canada
- Seaver Foundation, USA
- Swedish Science Council
- Centre for Applied Genomics, Canada
- Utah Autism Foundation, USA
- Core [075491/Z/04]
- Wellcome Trust, UK
- Division of Aging Biology, NIA
- Division of Geriatrics and Clinical Gerontology, NIA
- NIH [R01 NS36960]
- Michael J Fox Foundation
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Background: Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods: By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results: By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions: Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability.
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