Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis

Loh, Po-Ru and Bhatia, Gaurav and Gusev, Alexander and Finucane, Hilary K. and Bulik-Sullivan, Brendan K. and Pollack, Samuela J. and de Candia, Teresa R. and Lee, Sang Hong and Wray, Naomi R. and Kendler, Kenneth S. and O'Donovan, Michael C. and Neale, Benjamin M. and Patterson, Nick and Price, Alkes L. and Knight, Jo (2015) Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis. Nature Genetics, 47 (12). pp. 1385-1392. ISSN 1061-4036

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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.

Item Type:
Journal Article
Journal or Publication Title:
Nature Genetics
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1311
Subjects:
ID Code:
84453
Deposited By:
Deposited On:
30 Jan 2017 15:32
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Sep 2020 02:52