Bayesian survival analysis in genetic association studies

被引:3
|
作者
Tachmazidou, Ioanna [1 ]
Andrew, Toby [2 ]
Verzilli, Claudio J. [3 ]
Johnson, Michael R. [4 ]
De Iorio, Maria [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England
[2] Kings Coll London, Twin Res Unit, London SE1 7EH, England
[3] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England
[4] Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, London SW7 2AZ, England
基金
英国惠康基金;
关键词
D O I
10.1093/bioinformatics/btn351
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: Large-scale genetic association studies are carried out with the hope of discovering single nucleotide polymorphisms involved in the etiology of complex diseases. There are several existing methods in the literature for performing this kind of analysis for case-control studies, but less work has been done for prospective cohort studies. We present a Bayesian method for linking markers to censored survival outcome by clustering haplotypes using gene trees. Coalescent-based approaches are promising for LD mapping, as the coalescent offers a good approximation to the evolutionary history of mutations. Results: We compare the performance of the proposed method in simulation studies to the univariate Cox regression and to dimension reduction methods, and we observe that it performs similarly in localizing the causal site, while offering a clear advantage in terms of false positive associations. Moreover, it offers computational advantages. Applying our method to a real prospective study, we observe potential association between candidate ABC transporter genes and epilepsy treatment outcomes.
引用
收藏
页码:2030 / 2036
页数:7
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