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

Loh, Po-Ru, Bhatia, Gaurav, Gusev, Alexander, Finucane, Hilary K., Bulik-Sullivan, Brendan K., Pollack, Samuela J., de Candia, Teresa R., Lee, Sang Hong, Wray, Naomi R., Kendler, Kenneth S., O'Donovan, Michael C., Neale, Benjamin M., Patterson, Nick, Price, Alkes L., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Visscher, Peter M. and Mowry, Bryan J. (2015) Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis. Nature Genetics, 47 12: 1385-1392. doi:10.1038/ng.3431


Author Loh, Po-Ru
Bhatia, Gaurav
Gusev, Alexander
Finucane, Hilary K.
Bulik-Sullivan, Brendan K.
Pollack, Samuela J.
de Candia, Teresa R.
Lee, Sang Hong
Wray, Naomi R.
Kendler, Kenneth S.
O'Donovan, Michael C.
Neale, Benjamin M.
Patterson, Nick
Price, Alkes L.
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Visscher, Peter M.
Mowry, Bryan J.
Title Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1038/ng.3431
Volume 47
Issue 12
Start page 1385
End page 1392
Total pages 11
Place of publication New York, United States
Publisher Nature Publishing Group
Language eng
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.
Keyword Genome-Wide Association
Partitioning Heritability
Common Snps
Human Height
Risk Loci
Susceptibility
Metaanalysis
Inference
Traits
Information
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
 
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