Correcting "'Winner's Curse" in Odds Ratios from Genomewide Association Findings for Major Complex Human Diseases

被引:60
作者
Zhong, Hua [1 ]
Prentice, Ross L. [2 ]
机构
[1] Rosetta Inpharmat LLC, Dept Genet, Seattle, WA 98109 USA
[2] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA
关键词
bias correction; odds ratio; confidence interval; genomewide association study; complex human disease; CANCER SUSCEPTIBILITY LOCI; WIDE ASSOCIATION; COLORECTAL-CANCER; BREAST-CANCER; PROSTATE-CANCER; LUNG-CANCER; RISK LOCUS; 8Q24; VARIANTS; SCAN;
D O I
10.1002/gepi.20437
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Genome-wide association studies (GWAS) provide an important approach for identifying common genetic variants that predispose to human disease. However, odds ratio (OR) estimates for the reported findings from GWAS discovery data are typically affected by a bias away from the null sometimes referred to the "winner's curse". Also standard confidence intervals (CIs) may have far from the desired coverage rates. We applied a bias reduction method to GWAS findings from several major complex human diseases, including breast cancer, colorectal cancer, lung cancer, prostate cancer, type I diabetes, and type II diabetes. We found the simple bias correction procedure allows one to estimate bias-adjusted ORs that have substantial consistency with ORs from subsequent replication studies, and that corresponding selection-adjusted Cls appear to help quantify the uncertainty of the findings. Selection-adjusted ORs and Cls can provide a reliable summary of GWAS data, and can help to choose single nucleotide polymorphisms for subsequent validation studies. Genet. Epidemiol. 34:78-91, 2010. (c) 2009 Wiley-Liss, Inc.
引用
收藏
页码:78 / 91
页数:14
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