| Literature DB >> 35982160 |
Jack M Fu1,2,3, F Kyle Satterstrom2,4,5, Minshi Peng6, Harrison Brand1,2,3,7, Ryan L Collins1,2,3,8, Shan Dong9, Brie Wamsley10, Lambertus Klei11, Lily Wang2,8, Stephanie P Hao1,3,7, Christine R Stevens2,4,5, Caroline Cusick4, Mehrtash Babadi12, Eric Banks12, Brett Collins13,14,15, Sheila Dodge16, Stacey B Gabriel16, Laura Gauthier12, Samuel K Lee12, Lindsay Liang9, Alicia Ljungdahl9, Behrang Mahjani13,14,17, Laura Sloofman13,14,15, Andrey N Smirnov12, Mafalda Barbosa15,18, Catalina Betancur19, Alfredo Brusco20,21, Brian H Y Chung22, Edwin H Cook23, Michael L Cuccaro24, Enrico Domenici25, Giovanni Battista Ferrero26, J Jay Gargus27, Gail E Herman28, Irva Hertz-Picciotto29, Patricia Maciel30, Dara S Manoach31, Maria Rita Passos-Bueno32, Antonio M Persico33, Alessandra Renieri34,35,36, James S Sutcliffe37,38, Flora Tassone29,39, Elisabetta Trabetti40, Gabriele Campos32, Simona Cardaropoli26, Diana Carli26, Marcus C Y Chan22, Chiara Fallerini34,35, Elisa Giorgio20, Ana Cristina Girardi32, Emily Hansen-Kiss41, So Lun Lee22, Carla Lintas42, Yunin Ludena29, Rachel Nguyen27, Lisa Pavinato20, Margaret Pericak-Vance24, Isaac N Pessah29,43, Rebecca J Schmidt29, Moyra Smith27, Claudia I S Costa32, Slavica Trajkova20, Jaqueline Y T Wang32, Mullin H C Yu22, David J Cutler44, Silvia De Rubeis13,14,15,45, Joseph D Buxbaum46,47,48,49,50,51, Mark J Daly52,53,54,55,56,57, Bernie Devlin58, Kathryn Roeder59,60, Stephan J Sanders61, Michael E Talkowski62,63,64,65,66.
Abstract
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. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.Entities:
Mesh：
Year: 2022 PMID： 35982160 DOI： 10.1038/s41588-022-01104-0
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307