Mixture model-based association analysis with case-control data in genome wide association studies

Ali Fadhaa and Zhang Jian ()
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Ali Fadhaa: Department of Statistics, College of Administration and Economics, University of Baghdad, Baghdad, Iraq
Zhang Jian: School of Mathematics, Statistics and Actuarial Science, University of Kent, Canterbury, Kent CT2 7NF, UK

Statistical Applications in Genetics and Molecular Biology, 2017, vol. 16, issue 3, 173-187

Abstract: Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.

Keywords: genome wide association studies; haplotype mixture model; odds ratios; testing for inheritance patterns (search for similar items in EconPapers)
Date: 2017
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DOI: 10.1515/sagmb-2016-0022

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