4.8 Article

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

期刊

NATURE GENETICS
卷 45, 期 10, 页码 1150-+

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2742

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资金

  1. NIMH [R01 MH077139, R01 MH095034]
  2. Stanley Center for Psychiatric Research
  3. Sylvan Herman Foundation
  4. Friedman Brain Institute at the Mount Sinai School of Medicine
  5. Karolinska Institutet, Karolinska University Hospital
  6. Swedish Research Council
  7. Swedish County Council
  8. Soderstrom Konigska Foundation
  9. Netherlands Scientific Organization [NWO 645-000-003]
  10. European Union [HEALTH-F2-2009-223423]
  11. Danish Strategic Research Council
  12. H. Lundbeck A/S
  13. Faculty of Health Sciences at Aarhus University
  14. Lundbeck Foundation
  15. Stanley Research Foundation
  16. Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z]
  17. MRC [G0800509, G0701420, G0400126, G0600429, G1000718, G0901310, G1100583, G0601635] Funding Source: UKRI
  18. Medical Research Council [G0801418B, G0600429, G0601635, G1100583, G0901310, G0701420, G0400126, G1000718, G0800509] Funding Source: researchfish
  19. National Institute for Health Research [PDA/02/06/016, NF-SI-0507-10379] Funding Source: researchfish

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Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

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