Mapping genomic loci implicates genes and synaptic biology in schizophrenia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10442851" target="_blank" >RIV/00064165:_____/22:10442851 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/22:10442851 RIV/00216208:11110/22:10442851 RIV/00216208:11130/22:10442851
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=aCynLDYF8d" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=aCynLDYF8d</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41586-022-04434-5" target="_blank" >10.1038/s41586-022-04434-5</a>
Alternative languages
Result language
angličtina
Original language name
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Original language description
Schizophrenia 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature
ISSN
0028-0836
e-ISSN
1476-4687
Volume of the periodical
604
Issue of the periodical within the volume
7906
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
502-508
UT code for WoS article
000779867500004
EID of the result in the Scopus database
2-s2.0-85127650703