Journal article

All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs

Andrew J Schork, Wesley K Thompson, Phillip Pham, Ali Torkamani, J Cooper Roddey, Patrick F Sullivan, John R Kelsoe, Michael C O'Donovan, Helena Furberg, Nicholas J Schork, Ole A Andreassen, Anders M Dale

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2013

Open access

Abstract

Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1-FDR) for strata determined by different genic categories. We show a consistent pattern of enri..

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Funding Acknowledgements

AJS was supported by NIH grants RC2DA029475 and R01HD061414 and by the Robert J. Glushko and Pamela Samuelson Graduate Fellowship. WKT was supported by NIA grant SR01AG022381-09. PP, AT, and NJS were supported in part by NIH/NCRR grant number UL1 RR025774. OAA was supported by the Research Council of Norway (183782/V50) and the South East Norway Health Authority (2010-074). AMD was supported by NIH grants RC2DA029475, R01EB000790, R01AG031224, R01AG022381, P50MH081755, P50NS022343, and U54NS056883. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.