{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou X"],"funding":["Howard Hughes Medical Institute","NIMH NIH HHS","NIDCD NIH HHS","NIGMS NIH HHS"],"pagination":["1305-1319"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9470534"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["54(9)"],"pubmed_abstract":["To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10<sup>-6</sup>), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and S"],"journal":["Nature genetics"],"pubmed_title":["Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes."],"pmcid":["PMC9470534"],"funding_grant_id":["T32 GM008629","R01 MH105527","R01 DC014489","T32 GM139776","K99 MH117165","R01 MH101221","R01 GM120609"],"pubmed_authors":["Shu C","Dillon E","Stephens AN","Turner TN","Cordova J","Edmonson C","Abbeduto L","Lillie N","Erickson CA","Gunter C","Obiajulu JU","Manning P","Daniels AM","Weaver WC","Russell N","Berger N","Xu S","Dennis MY","Qi H","Hale MN","White S","Roche C","Polite J","Lopez M","Tso IF","Mathai S","Morrier MJ","Piven J","Pama K","Baer M","Cartner LA","Plate S","Bashar A","Fox EA","Beckwith M","Berman A","Pawlowski 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S","Holbrook A","Rutter T","Baraghoshi G","Huang-Storms LY","Hojlo M","Law JK","Jou R","Michaelson JJ","Wasserburg L","Colombi C","Feliciano P","Yang WS","Shocklee AD","Ho T","Heydemann P","Boland S","Coughlin M","Real K","Rodriguez N","Fatemi A","Long N","Eldred S","Madi N","Hooks G","Marchenko O","Baalman K","Beeson L","Gong J","Littlefield S","Geschwind DH","Beeson J","Robertson BE","Koomar T","Orobio J","Palmer S","Licona S","Ghina H","Rambeck D","Kitaygorodsky A","Harvey WT","Coppola L","Brown J","Arriaga I","Warren ZE","Shikov R"],"additional_accession":[]},"is_claimable":false,"name":"Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes.","description":"To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10<sup>-6</sup>), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and S","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-04-19T00:29:38.211Z","creation":"2025-04-07T11:34:16.173Z"},"accession":"S-EPMC9470534","cross_references":{"pubmed":["35982159"],"doi":["10.1038/s41588-022-01148-2"]}}