Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Vassily Trubetskoy, Antonio F. Pardiñas, Ting Qi, Georgia Panagiotaropoulou, Swapnil Awasthi, Tim B. Bigdeli, Julien Bryois, Chia‐Yen Chen, Charlotte Dennison, Lynsey S. Hall, Max Lam, Kyoko Watanabe, Oleksandr Frei, Tian Ge, Janet Harwood, Frank Koopmans, Sigurður H. Magnússon, Alexander Richards, Julia Sidorenko, Yang Wu, Jian Zeng, Jakob Grove, Minsoo Kim, Zhiqiang Li, Georgios Voloudakis, Wen Zhang, Mark J. Adams, Ingrid Agartz, Elizabeth G. Atkinson, Esben Agerbo, Mariam Al Eissa, Margot Albus, Madeline Alexander, Behrooz Z. Alizadeh, Köksal Alptekın, Thomas D. Als, Farooq Amin, Volker Arolt, Manuel Arrojo, Lavinia Athanasiu, M.H. Azevedo, Silviu‐Alin Bacanu, Nicholas Bass, Martin Begemann, Richard A. Belliveau, Judit Bene, Beben Benyamin, Sarah E. Bergen, Giuseppe Blasi, Julio Bobes, Stefano Bonassi, Alice Braun, Rodrigo A. Bressan, Evelyn J. Bromet, Richard Bruggeman, P.F. Buckley, Randy L. Buckner, Jonas Bybjerg‐Grauholm, Wiepke Cahn, Murray J. Cairns, Monica E. Calkins, Vaughan J. Carr, David Castle, Stanley V. Catts, Kimberley D. Chambert, Raymond Chan, Boris Chaumette, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, David Cohen, Angèle Consoli, Quirino Cordeiro, Javier Costas, Charles Curtis, Michael Davidson, Kenneth L. Davis, Lieuwe de Haan, Franziska Degenhardt, Lynn E. DeLisi, Ditte Demontis, Faith Dickerson, Dimitris Dikeos, Timothy G. Dinan, Srdjan Djurovic, Jubao Duan, Giuseppe Ducci, Frank Dudbridge, Johan G. Eriksson, Lourdes Fañanás, Stephen V. Faraone, Alessia Fiorentino, Andreas J. Forstner, Josef Frank, Nelson B. Freimer, Menachem Fromer, Alessandra Frustaci, Ary Gadelha, Giulio Genovese, Elliot S. Gershon

Nature · 2022

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Summary

Schizophrenia has a heritability of 60-80%<sup>1</sup>, 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

Source type
Peer-reviewed study
DOI
10.1038/s41586-022-04434-5
Catalogue ID
SNmohi6g1u-v9jxya
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