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Mixture Model-Based Association Analysis with Case-Control Data in Genome Wide Association Studies

Ali, Fadhaa, Zhang, Jian (2017) Mixture Model-Based Association Analysis with Case-Control Data in Genome Wide Association Studies. Statistical Applications in Genetics and Molecular Biology, 16 (3). pp. 173-187. ISSN 2194-6302. E-ISSN 1544-6115. (doi:10.1515/sagmb-2016-0022) (KAR id:51225)


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 simulation results show that the proposed approach outperforms an existing multiple testing method in terms of average specificity and sensitivity. We apply the proposed approach to analyzing two datasets on coronary artery disease and hypertension in the Wellcome Trust Case Control Consortium, identifying many more disease associated haplotype blocks than does the existing method.

Item Type: Article
DOI/Identification number: 10.1515/sagmb-2016-0022
Uncontrolled keywords: Genome wide association studies; haplotype mixture model; testing for inheritance patterns; odds ratios
Subjects: Q Science > QA Mathematics (inc Computing science) > QA276 Mathematical statistics
Divisions: Divisions > Division of Computing, Engineering and Mathematical Sciences > School of Mathematics, Statistics and Actuarial Science
Depositing User: Jian Zhang
Date Deposited: 25 Oct 2015 19:12 UTC
Last Modified: 09 Dec 2022 04:11 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Ali, Fadhaa.

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Zhang, Jian.

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