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

  • Fadhaa Ali and Jian Zhang EMAIL logo
Published/Copyright: July 19, 2017

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.

Acknowledgement

We thank the WTCCC for sharing their data with us. The project was partially done when the second author was visiting Chinese Academy of Sciences, Beijing. The second author thanks Professor Guohua Zou for his hospitality. The research of the first author was funded by the Ministry of Higher Education and Scientific Research, Iraq. The authors have no conflicts of interest to declare.

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Supplemental Material:

The online version of this article (DOI: https://doi.org/10.1515/sagmb-2016-0022) offers supplementary material, available to authorized users.


Published Online: 2017-7-19
Published in Print: 2017-7-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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