Rare coding variation provides insight into the genetic architecture and phenotypic context of autism
| Title: | Rare coding variation provides insight into the genetic architecture and phenotypic context of autism |
|---|---|
| Authors: | Fu JM; Satterstrom FK; Peng M; Brand H; Collins RL; Dong S; Wamsley B; Klei L; Wang L; Hao SP; Stevens CR; Cusick C; Babadi M; Banks E; Collins B; Dodge S; Gabriel SB; Gauthier L; Lee SK; Liang L; Ljungdahl A; Mahjani B; Sloofman L; Smirnov AN; Barbosa M; Betancur C; Brusco A; Chung BHY; Cook EH; Cuccaro ML; Domenici E; Ferrero GB; Gargus JJ; Herman GE; Hertz-Picciotto I; Maciel P; Manoach DS; Passos-Bueno MR; Persico AM; Renieri A; Sutcliffe JS; Tassone F; Trabetti E; Campos G; Cardaropoli S; Carli D; Chan MCY; Fallerini C; Giorgio E; Girardi AC; Hansen-Kiss E; Lee SL; Lintas C; Ludena Y; Nguyen R; Pavinato L; Pericak-Vance M; Pessah IN; Schmidt RJ; Smith M; Costa CIS; Trajkova S; Wang JYT; Yu MHC; Autism Sequencing Consortium (ASC); Broad Institute Center for Common Disease Genomics (Broad-CCDG); iPSYCH-BROAD Consortium; Cutler DJ; De Rubeis S; Buxbaum JD; Daly MJ; Devlin B; Roeder K; Sanders SJ; Talkowski ME. |
| Contributors: | Fu, Jm; Satterstrom, Fk; Peng, M; Brand, H; Collins, Rl; Dong, S; Wamsley, B; Klei, L; Wang, L; Hao, Sp; Stevens, Cr; Cusick, C; Babadi, M; Banks, E; Collins, B; Dodge, S; Gabriel, Sb; Gauthier, L; Lee, Sk; Liang, L; Ljungdahl, A; Mahjani, B; Sloofman, L; Smirnov, An; Barbosa, M; Betancur, C; Brusco, A; Chung, Bhy; Cook, Eh; Cuccaro, Ml; Domenici, E; Ferrero, Gb; Gargus, Jj; Herman, Ge; Hertz-Picciotto, I; Maciel, P; Manoach, D; Passos-Bueno, Mr; Persico, Am; Renieri, A; Sutcliffe, J; Tassone, F; Trabetti, E; Campos, G; Cardaropoli, S; Carli, D; Chan, Mcy; Fallerini, C; Giorgio, E; Girardi, Ac; Hansen-Kiss, E; Lee, Sl; Lintas, C; Ludena, Y; Nguyen, R; Pavinato, L; Pericak-Vance, M; Pessah, In; Schmidt, Rj; Smith, M; Costa, Ci; Trajkova, S; Wang, Jyt; Yu, Mhc; Autism Sequencing Consortium, (ASC); Broad Institute Center for Common Disease Genomics, (Broad-CCDG); iPSYCH-BROAD, Consortium; Cutler, Dj; De Rubeis, S; Buxbaum, Jd; Daly, Mj; Devlin, B; Roeder, K; Sanders, Sj; Talkowski, Me. |
| Publication Year: | 2022 |
| Collection: | Università degli Studi di Verona: Catalogo dei Prodotti della Ricerca (IRIS) |
| Subject Terms: | Autism spectrum disorders; Gene expression; Genetic association study; Neurodevelopmental disorders |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| File Description: | STAMPA |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/35982160; info:eu-repo/semantics/altIdentifier/wos/WOS:000842689300001; volume:54; issue:9; firstpage:1320; lastpage:1331; numberofpages:12; journal:NATURE GENETICS; https://hdl.handle.net/11562/1073647 |
| DOI: | 10.1038/s41588-022-01104-0 |
| Availability: | https://hdl.handle.net/11562/1073647; https://doi.org/10.1038/s41588-022-01104-0 |
| Accession Number: | edsbas.6A270D6B |
| Database: | BASE |