Statistical Applications in Genetics and Molecular Biology
Editor-in-Chief: Stumpf, Michael P.H.
6 Issues per year
IMPACT FACTOR 2016: 0.646
5-year IMPACT FACTOR: 1.191
CiteScore 2016: 0.94
SCImago Journal Rank (SJR) 2016: 0.625
Source Normalized Impact per Paper (SNIP) 2016: 0.596
Mathematical Citation Quotient (MCQ) 2016: 0.06
Non-Iterative, Regression-Based Estimation of Haplotype Associations with Censored Survival Outcomes
The general availability of reliable and affordable genotyping technology has enabled genetic association studies to move beyond small case-control studies to large prospective studies. For prospective studies, genetic information can be integrated into the analysis via haplotypes, with focus on their association with a censored survival outcome. We develop non-iterative, regression-based methods to estimate associations between common haplotypes and a censored survival outcome in large cohort studies. Our non-iterative methods—weighted estimation and weighted haplotype combination—are both based on the Cox regression model, but differ in how the imputed haplotypes are integrated into the model. Our approaches enable haplotype imputation to be performed once as a simple data-processing step, and thus avoid implementation based on sophisticated algorithms that iterate between haplotype imputation and risk estimation. We show that non-iterative weighted estimation and weighted haplotype combination provide valid tests for genetic associations and reliable estimates of moderate associations between common haplotypes and a censored survival outcome, and are straightforward to implement in standard statistical software. We apply the methods to an analysis of HSPB7-CLCNKA haplotypes and risk of adverse outcomes in a prospective cohort study of outpatients with chronic heart failure.
Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.