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Title: Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis
Contributor(s): Loh, Po-Ru (author); Bhatia, Gaurav (author); O'Donovan, Michael C (author); Neale, Benjamin M (author); Patterson, Nick (author); Price, Alkes L (author); Gusev, Alexander (author); Finucane, Hilary K (author); Bulik-Sullivan, Brendan K (author); Pollack, Samuela J (author); de Candia, Teresa R (author); Lee, Sang Hong  (author); Wray, Naomi R (author); Kendler, Kenneth S (author)
Publication Date: 2015
Open Access: Yes
DOI: 10.1038/ng.3431Open Access Link
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Abstract: Heritability analyses of genome-wide association study (GWAS) cohorts have yielded important insights into complex disease architecture, and increasing sample sizes hold the promise of further discoveries. Here we analyze the genetic architectures of schizophrenia in 49,806 samples from the PGC and nine complex diseases in 54,734 samples from the GERA cohort. For schizophrenia, we infer an overwhelmingly polygenic disease architecture in which ≥71% of 1-Mb genomic regions harbor ≥1 variant influencing schizophrenia risk. We also observe significant enrichment of heritability in GC-rich regions and in higher-frequency SNPs for both schizophrenia and GERA diseases. In bivariate analyses, we observe significant genetic correlations (ranging from 0.18 to 0.85) for several pairs of GERA diseases; genetic correlations were on average 1.3 tunes stronger than the correlations of overall disease liabilities. To accomplish these analyses, we developed a fast algorithm for multicomponent, multi-trait variance-components analysis that overcomes prior computational barriers that made such analyses intractable at this scale.
Publication Type: Journal Article
Source of Publication: Nature Genetics, 47(12), p. 1385-1392
Publisher: Nature Publishing Group
Place of Publication: United States of America
ISSN: 1546-1718
Fields of Research (FoR) 2008: 060499 Genetics not elsewhere classified
060408 Genomics
060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
Fields of Research (FoR) 2020: 310599 Genetics not elsewhere classified
310509 Genomics
310506 Gene mapping
Socio-Economic Objective (SEO) 2008: 970106 Expanding Knowledge in the Biological Sciences
970108 Expanding Knowledge in the Information and Computing Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
Socio-Economic Objective (SEO) 2020: 280102 Expanding knowledge in the biological sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article

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