Survival Analysis Methods in Genetic Epidemiology

Abstract

Mapping genes for complex human diseases is a challenging problem due to the fact that many such diseases are due to both genetic and enviromental risk factors and many also exhibit phenotypic heterogeneity, such as variable age of onset. Information on variable age of disease onset is often a good indicator for disease heterogeneity and incorporation of such information together with enviromental risk factors into genetic analysis should lead to more powerful tests for genetic analysis. Due to the problem of censoring, survival analysis methods have proved to be very useful for genetic analysis. In this paper, I review some recent methodological developments on integrating modern survival analysis methods and human genetics in order to rigorously incorporate both age of onset and enviromental covariates data into aggregation analysis, segregation analysis, linkage analysis, association analysis and gene risk characterization. I also briefly discuss the issue of ascertainment correction and survival analysis methods for high-dimensional genomic data. Finally, I outline several areas that need further methodological developments. Survival Analysis Methods in Genetic Epidemiology Running title: Survival Analysis Methods A Chapter in ”Current Topics in Human Genetics: Studies of Complex Diseases” (Eds. Hong-Wen Deng, Hui Shen, Yongjun Liu, Hai Hu) Hongzhe Li Professor of Biostatistics Department of Biostatistics and Epidemiology University of Pennsylvania School of Medicine Philadelphia, PA 19104-6021, USA Email: hli@cceb.upenn.edu 0 Hosted by The Berkeley Electronic Press