000907296 001__ 907296
000907296 005__ 20230502100727.0
000907296 0247_ $$2doi$$a10.1038/s41586-022-04434-5
000907296 0247_ $$2ISSN$$a0028-0836
000907296 0247_ $$2ISSN$$a1476-4687
000907296 0247_ $$2Handle$$a2128/33199
000907296 0247_ $$2pmid$$a35396580
000907296 0247_ $$2WOS$$aWOS:000779867500004
000907296 037__ $$aFZJ-2022-01947
000907296 082__ $$a500
000907296 1001_ $$aTrubetskoy, Vassily$$b0
000907296 245__ $$aMapping genomic loci implicates genes and synaptic biology in schizophrenia
000907296 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2022
000907296 3367_ $$2DRIVER$$aarticle
000907296 3367_ $$2DataCite$$aOutput Types/Journal article
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000907296 3367_ $$2BibTeX$$aARTICLE
000907296 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000907296 3367_ $$00$$2EndNote$$aJournal Article
000907296 520__ $$aSchizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.
000907296 536__ $$0G:(DE-HGF)POF4-5251$$a5251 - Multilevel Brain Organization and Variability (POF4-525)$$cPOF4-525$$fPOF IV$$x0
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000907296 7001_ $$aQi, Ting$$b2
000907296 7001_ $$aPanagiotaropoulou, Georgia$$b3
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