title: Testing for association in case-control genome-wide association studies with shared controls.
abstract: The statistical analysis of genome-wide association studies (GWASs) with multiple diseases and shared controls (SCs) is discussed. The usual method for analyzing data from these studies is to compare each individual disease with either the SCs or the pooled controls which include other diseases. We observed that applying individual association tests can be problematic because these tests may suffer from power loss in detecting significant associations between diseases and single-nucleotide polymorphism or copy number variant. We propose here a two-stage procedure wherein we first apply an overall chi-square test for multiple diseases with SCs; if the overall test is rejected, then individual tests using the chi-square partition method will be applied to each disease against SCs. A real GWAS data set with SCs and a Monte Carlo simulation study are used to demonstrate that the proposed method is more effective and preferable than other existing methods for analyzing data from GWASs with multiple diseases and SCs.
authors: Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, IN, USA zc3@indiana.edu.
authors: Zhongxue
authors: Z
authors: Chen
authors: Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors: Hanwen
authors: H
authors: Huang
authors: Department of Statistical Science, Southern Methodist University, Dallas, TX, USA.
authors: Hon Keung Tony
authors: HK
authors: Ng
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D056915:DNA Copy Number Variations; D055106:Genome-Wide Association Study / Q000379:methods* / Q000592:standards; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D009010:Monte Carlo Method; D009103:Multiple Sclerosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics; D013967:Thyroiditis, Autoimmune / Q000235:genetics; D006113:United Kingdom
keywords: Cochran–Armitage trend test; chi-square partition; robust test; single-nucleotide polymorphism