Bayesian survival analysis in genetic association studies
File(s)
Author(s)
Tachmazidou, Ioanna
Andrew, Toby
Verzilli, Claudio J
Johnson, Michael R
De Iorio, Maria
Type
Journal Article
Abstract
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.
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.
Date Issued
2008-09-15
Date Acceptance
2008-07-08
Citation
Bioinformatics, 2008, 24 (18), pp.2030-2036
ISSN
1367-4803
Publisher
Oxford University Press (OUP)
Start Page
2030
End Page
2036
Journal / Book Title
Bioinformatics
Volume
24
Issue
18
Copyright Statement
© 2008 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Subjects
Science & Technology
Life Sciences & Biomedicine
Technology
Physical Sciences
Biochemical Research Methods
Biotechnology & Applied Microbiology
Computer Science, Interdisciplinary Applications
Mathematical & Computational Biology
Statistics & Probability
Biochemistry & Molecular Biology
Computer Science
Mathematics
MULTIDRUG-RESISTANCE
DRUG-RESISTANCE
P-GLYCOPROTEIN
EPILEPSY
ABCB1
POLYMORPHISM
HAPLOTYPE
PREDICTION
TREES
Publication Status
Published
Date Publish Online
2008-07-09