{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singh T"],"funding":["NICHD NIH HHS","NIDA NIH HHS","NIA NIH HHS","NIMH NIH HHS","Medical Research Council","NHLBI NIH HHS","NHGRI NIH HHS","NIAAA NIH HHS","Lundbeck Foundation","NIH HHS"],"pagination":["509-516"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9805802"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["604(7906)"],"pubmed_abstract":["Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10<sup>-6</sup>) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glu"],"journal":["Nature"],"pubmed_title":["Rare coding variants in ten genes confer substantial risk for schizophrenia."],"pmcid":["PMC9805802"],"funding_grant_id":["U01 HL117626","R01 MH085548","R01 AA009367","R01 DA005147","R01 HL117626","U01 MH105578","R01 MH094145","U01 MH105653","R01 MH116037","R01 MH104964","U01 MH109539","MR/L010305/1","R01 MH085521","R155-2014-1724","R248-2017-2003","R01 AG064955","R204-2015-4129","R01 MH124851","R24-2008-3243","G0800509","R341-2020-222","R01 DA037904","U54 HG003067","U01 MH105666","P50 HD105351","U01 MH105641","U01 DA024417","R01 MH123451","R37 DA005147","R37 AA009367","R01 DA036216","5R01 AG06495502","R364-2021-85","R01 DA024417","R01 HG007022"],"pubmed_authors":["Kahn RS","Bybjerg-Grauholm J","Vawter MP","Francioli L","Faraone SV","Palotie A","Kirov G","Gabriel SB","Sullivan PF","Kang HM","Satterstrom FK","Hamalainen E","Esko T","Milani L","Watts NA","Malaspina D","Genovese G","Bigdeli TB","Holi M","Chen WJ","Neale BM","Bass N","Morris DW","Daly MJ","Buckley PF","O'Donovan MC","Palmer DS","Sklar P","DeLisi L","Gagliano Taliun SA","Marder SR","Ouwehand WH","Glahn DC","Corvin AP","Myers RM","Curtis D","Dodge S","Ganna A","Ongur D","St Clair D","Grove J","Hultman CM","O'Brien NL","Poterba T","Boehnke M","Blackwood DH","Scott LJ","Heyne HO","Tsuang MT","Barchas JD","Suvisaari J","Byerley WF","Howrigan DP","Huang H","Fanous AH","Karczewski KJ","Rees E","Werge TM","Morley CP","Nordentoft M","Smoller JW","Eskelinen S","Singh T","Watson SJ","Lehrer DS","Churchhouse C","Hwu HG","Tiao G","Breen G","Medeiros H","Ophoff RA","Hall MH","Cusick CM","Bromet EJ","Mortensen PB","Pato CN","Owen MJ","McCarroll SA","Stevens CR","Al Eissa M","Cohen BM","Hougaard DM","Walters JT","Paunio T","Schatzberg A","Glatt SJ","Knowles JA","Bunney WE","Borglum AD","Escamilla MA","Chapman SB","Gage D","Akil H","McIntosh AM","Olivares AM","Freimer NB","Scolnick E","Pulver AE","Fiorentino A","Sharp SI","Rollins B","Solomonson M","McQuillin A","Lee FS","Rapaport MH","Quested D","Craddock N","Sobell JL","Pato MT","Lescai F","Stahl EA"],"additional_accession":[]},"is_claimable":false,"name":"Rare coding variants in ten genes confer substantial risk for schizophrenia.","description":"Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10<sup>-6</sup>) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glu","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-28T06:10:06.414Z","creation":"2025-04-05T23:29:21.778Z"},"accession":"S-EPMC9805802","cross_references":{"pubmed":["35396579"],"doi":["10.1038/s41586-022-04556-w"]}}