Bayesian Semiparametric Meta-Analysis for Genetic Association Studies


de Iorio, M; Newcombe, PJ; Tachmazidou, I; Verzilli, CJ; Whittaker, JC; (2011) Bayesian Semiparametric Meta-Analysis for Genetic Association Studies. Genetic epidemiology, 35 (5). pp. 333-340. ISSN 0741-0395 DOI: https://doi.org/10.1002/gepi.20581

Full text not available from this repository. (Request a copy)

Abstract

We present a Bayesian semiparametric model for the meta-analysis of candidate gene studies with a binary outcome. Such studies often report results from association tests for different, possibly study-specific and non-overlapping genetic markers in the same genetic region. Meta-analyses of the results at each marker in isolation are seldom appropriate as they ignore the correlation that may exist between markers due to linkage disequilibrium (LD) and cannot assess the relative importance of variants at each marker. Also such marker-wise meta-analyses are restricted to only those studies that have typed the marker in question, with a potential loss of power. A better strategy is one which incorporates information about the LD between markers so that any combined estimate of the effect of each variant is corrected for the effect of other variants, as in multiple regression. Here we develop a Bayesian semiparametric model which models the observed genotype group frequencies conditional to the case/control status and uses pairwise LD measurements between markers as prior information to make posterior inference on adjusted effects. The approach allows borrowing of strength across studies and across markers. The analysis is based on a mixture of Dirichlet processes model as the underlying semiparametric model. Full posterior inference is performed through Markov chain Monte Carlo algorithms. The approach is demonstrated on simulated and real data. Genet. Epidemiol. 35: 333-340, 2011. (C) 2011 Wiley-Liss, Inc.

Item Type: Article
Keywords: delta method, Dirichlet process, linkage disequilibrium, multivariate, multinomial logit distribution, SNP data, GENOME-WIDE ASSOCIATION, 5-LIPOXYGENASE ACTIVATING PROTEIN, ISCHEMIC-STROKE, PHOSPHODIESTERASE 4D, PDE4D GENE, HAPLOTYPE MAP, CONFERS RISK, POPULATION, DISEASE, REGION
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Statistical Methodology
PubMed ID: 21400586
Web of Science ID: 291591100005
URI: http://researchonline.lshtm.ac.uk/id/eprint/564

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
296Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item