Singh, TarjinderTarjinderSinghPoterba, TimothyTimothyPoterbaCurtis, DavidDavidCurtisAkil, HudaHudaAkilAl Eissa, MariamMariamAl EissaBarchas, Jack DJack DBarchasBass, NicholasNicholasBassBigdeli, Tim BTim BBigdeliBreen, GeromeGeromeBreenBromet, Evelyn JEvelyn JBrometBuckley, Peter FPeter FBuckleyBunney, William EWilliam EBunneyBybjerg-Grauholm, JonasJonasBybjerg-GrauholmByerley, William FWilliam FByerleyChapman, Sinéad BSinéad BChapmanWEI J. CHENChurchhouse, ClaireClaireChurchhouseCraddock, NicholasNicholasCraddockCusick, Caroline MCaroline MCusickDeLisi, LynnLynnDeLisiDodge, SheilaSheilaDodgeEscamilla, Michael AMichael AEscamillaEskelinen, SaanaSaanaEskelinenFanous, Ayman HAyman HFanousFaraone, Stephen VStephen VFaraoneFiorentino, AlessiaAlessiaFiorentinoFrancioli, LaurentLaurentFrancioliGabriel, Stacey BStacey BGabrielGage, DianeDianeGageGagliano Taliun, Sarah ASarah AGagliano TaliunGanna, AndreaAndreaGannaGenovese, GiulioGiulioGenoveseGlahn, David CDavid CGlahnGrove, JakobJakobGroveHall, Mei-HuaMei-HuaHallHämäläinen, EijaEijaHämäläinenHeyne, Henrike OHenrike OHeyneHoli, MattiMattiHoliHougaard, David MDavid MHougaardHowrigan, Daniel PDaniel PHowriganHuang, HailiangHailiangHuangHwu, Hai-GwoHai-GwoHwuKahn, René SRené SKahnKang, Hyun MinHyun MinKangKarczewski, Konrad JKonrad JKarczewskiKirov, GeorgeGeorgeKirovKnowles, James AJames AKnowlesLee, Francis SFrancis SLeeLehrer, Douglas SDouglas SLehrerLescai, FrancescoFrancescoLescaiMalaspina, DoloresDoloresMalaspinaMarder, Stephen RStephen RMarderMcCarroll, Steven ASteven AMcCarrollMcIntosh, Andrew MAndrew MMcIntoshMedeiros, HelenaHelenaMedeirosMilani, LiliLiliMilaniMorley, Christopher PChristopher PMorleyMorris, Derek WDerek WMorrisMortensen, Preben BoPreben BoMortensenMyers, Richard MRichard MMyersNordentoft, MereteMereteNordentoftO'Brien, Niamh LNiamh LO'BrienOlivares, Ana MariaAna MariaOlivaresOngur, DostDostOngurOuwehand, Willem HWillem HOuwehandPalmer, Duncan SDuncan SPalmerPaunio, TiinaTiinaPaunioQuested, DigbyDigbyQuestedRapaport, Mark HMark HRapaportRees, ElliottElliottReesRollins, BrandiBrandiRollinsSatterstrom, F KyleF KyleSatterstromSchatzberg, AlanAlanSchatzbergScolnick, EdwardEdwardScolnickScott, Laura JLaura JScottSharp, Sally ISally ISharpSklar, PamelaPamelaSklarSmoller, Jordan WJordan WSmollerSobell, Janet LJanet LSobellSolomonson, MatthewMatthewSolomonsonStahl, Eli AEli AStahlStevens, Christine RChristine RStevensSuvisaari, JaanaJaanaSuvisaariTiao, GraceGraceTiaoWatson, Stanley JStanley JWatsonWatts, Nicholas ANicholas AWattsBlackwood, Douglas HDouglas HBlackwoodBørglum, Anders DAnders DBørglumCohen, Bruce MBruce MCohenCorvin, Aiden PAiden PCorvinEsko, TõnuTõnuEskoFreimer, Nelson BNelson BFreimerGlatt, Stephen JStephen JGlattHultman, Christina MChristina MHultmanMcQuillin, AndrewAndrewMcQuillinPalotie, AarnoAarnoPalotiePato, Carlos NCarlos NPatoPato, Michele TMichele TPatoPulver, Ann EAnn EPulverSt Clair, DavidDavidSt ClairTsuang, Ming TMing TTsuangVawter, Marquis PMarquis PVawterWalters, James TJames TWaltersWerge, Thomas MThomas MWergeOphoff, Roel ARoel AOphoffSullivan, Patrick FPatrick FSullivanOwen, Michael JMichael JOwenBoehnke, MichaelMichaelBoehnkeO'Donovan, Michael CMichael CO'DonovanNeale, Benjamin MBenjamin MNealeDaly, Mark JMark JDaly2023-03-212023-03-212022-040028-0836https://scholars.lib.ntu.edu.tw/handle/123456789/629552Rare 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 × 10-6) 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 glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.enMUTATIONS; INDIVIDUALS; ASSOCIATION; BURDENjournal article10.1038/s41586-022-04556-w353965792-s2.0-85127630161WOS:000779867500003https://api.elsevier.com/content/abstract/scopus_id/85127630161