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A subset-based approach improves power and interpretation for the combined analysis of genetic association studies of heterogeneous traits.

Authors
Bhattacharjee-S; Rajaraman-P; Jacobs-KB; Wheeler-WA; Melin-BS; Hartge-P; GliomaScan Consortium; Yeager-M; Chung-CC; Chanock-SJ; Chatterjee-N
Source
Am J Hum Genet 2012 May; 90(5):821-835
NIOSHTIC No.
20041784
Abstract
Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical approaches for meta-analysis or pooled analysis, however, might not be suitable for such analysis because individual variants are likely to be associated with only a subset of the traits or might demonstrate effects in different directions. We propose a method that exhaustively explores subsets of studies for the presence of true association signals that are in either the same direction or possibly opposite directions. An efficient approximation is used for rapid evaluation of p values. We present two illustrative applications, one for a meta-analysis of separate case-control studies of six distinct cancers and another for pooled analysis of a case-control study of glioma, a class of brain tumors that contains heterogeneous subtypes. Both the applications and additional simulation studies demonstrate that the proposed methods offer improved power and more interpretable results when compared to traditional methods for the analysis of heterogeneous traits. The proposed framework has applications beyond genetic association studies.
Keywords
Cancer; Brain-tumors; Genes; Genetic-factors; Heredity; Analytical-processes; Analytical-methods; Case-studies; Tumors; Statistical-analysis; Risk-analysis
Contact
Nilanjan Chatterjee, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, MD 20852, USA
CODEN
AJHGAG
Publication Date
20120501
Document Type
Journal Article
Email Address
chattern@mail.nih.gov
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B20121218C
Issue of Publication
5
ISSN
0002-9297
NIOSH Division
DART; DSHEFS
Source Name
American Journal of Human Genetics
State
MD; OH
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