A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex
| العنوان: | A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex |
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| المؤلفون: | Danny Antaki, James Guevara, Adam X. Maihofer, Marieke Klein, Madhusudan Gujral, Jakob Grove, Caitlin E. Carey, Oanh Hong, Maria J. Arranz, Amaia Hervas, Christina Corsello, Keith K. Vaux, Alysson R. Muotri, Lilia M. Iakoucheva, Eric Courchesne, Karen Pierce, Joseph G. Gleeson, Elise B. Robinson, Caroline M. Nievergelt, Jonathan Sebat |
| المصدر: | Nature genetics, vol 54, iss 9 Antaki, D, Guevara, J, Maihofer, A X, Klein, M, Gujral, M, Grove, J, Carey, C E, Hong, O, Arranz, M J, Hervas, A, Corsello, C, Vaux, K K, Muotri, A R, Iakoucheva, L M, Courchesne, E, Pierce, K, Gleeson, J G, Robinson, E B, Nievergelt, C M & Sebat, J 2022, ' A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex ', Nature Genetics, vol. 54, no. 9, pp. 1284-1292 . https://doi.org/10.1038/s41588-022-01064-5 |
| بيانات النشر: | eScholarship, University of California, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Pediatric, Multifactorial Inheritance, Autism Spectrum Disorder, Prevention, Intellectual and Developmental Disabilities (IDD), Autism, Neurosciences, Biological Sciences, Medical and Health Sciences, Brain Disorders, Mental Health, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Family, Female, Genetic Testing, Autistic Disorder, Aetiology, Child, Developmental Biology |
| الوصف: | The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but how combinations of genetic factors determine risk is unclear. In a large family sample, we show that genetic loads of rare and polygenic risk are inversely correlated in cases and greater in females than in males, consistent with a liability threshold that differs by sex. De novo mutations (DNMs), rare inherited variants and polygenic scores were associated with various dimensions of symptom severity in children and parents. Parental age effects on risk for ASD in offspring were attributable to a combination of genetic mechanisms, including DNMs that accumulate in the paternal germline and inherited risk that influences behavior in parents. Genes implicated by rare variants were enriched in excitatory and inhibitory neurons compared with genes implicated by common variants. Our results suggest that a phenotypic spectrum of ASD is attributable to a spectrum of genetic factors that impact different neurodevelopmental processes. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a71963f9ce1e59a9501c8acf3f96a067 https://escholarship.org/uc/item/5s6754zv |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a71963f9ce1e59a9501c8acf3f96a067 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |