Premium
P ‐value based analysis for shared controls design in genome‐wide association studies
Author(s) -
Zaykin Dmitri V.,
Kozbur Damian O.
Publication year - 2010
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20536
Subject(s) - association (psychology) , genetic association , statistic , genome wide association study , summary statistics , statistics , dependency (uml) , computer science , computational biology , biology , single nucleotide polymorphism , genetics , psychology , mathematics , artificial intelligence , genotype , psychotherapist , gene
An appealing genome‐wide association study design compares one large control group against several disease samples. A pioneering study by the Wellcome Trust Case Control Consortium that employed such a design has identified multiple susceptibility regions, many of which have been independently replicated. While reusing a control sample provides effective utilization of data, it also creates correlation between association statistics across diseases. An observation of a large association statistic for one of the diseases may greatly increase chances of observing a spuriously large association for a different disease. Accounting for the correlation is also particularly important when screening for SNPs that might be involved in a set of diseases with overlapping etiology. We describe methods that correct association statistics for dependency due to shared controls, and we describe ways to obtain a measure of overall evidence and to combine association signals across multiple diseases. The methods we describe require no access to individual subject data, instead, they efficiently utilize information contained in P ‐values for association reported for individual diseases. P ‐value based combined tests for association are flexible and essentially as powerful as the approach based on aggregating the individual subject data. Genet. Epidemiol . 34:725–738, 2010.© 2010 Wiley‐Liss, Inc.