Genetics. Published Articles Ahead of Print: April 19, 2006, Copyright © 2006
doi:10.1534/genetics.106.055921


A more recent version of this article appeared on July 1, 2006.

REGULAR RESEARCH PAPERS

A Simple Linear Regression Method For QTL Linkage Analysis With Censored Observations

Carl A Anderson 1*, Allan F McRae 2 and Peter M Visscher 2

1 University of Edinburgh
2 Queensland Institute of Medical Research

* To whom correspondence should be addressed. E-mail: carl.anderson{at}qimr.edu.au.

Submitted on January 17, 2006
Revised on March 17, 2006
Accepted on 14 April 2006


Abstract

Standard quantitative trait loci (QTL) mapping techniques commonly assume that the trait is both fully observed and normally distributed. When considering survival or age-at-onset traits these assumptions are often incorrect. Methods have been developed to map QTL for survival traits; however they are both computationally intensive and not available in standard genome analysis software packages. We propose a grouped linear regression method for the analysis of continuous survival data. Using simulation we compare this method to both the Cox and Weibull proportional hazards models and a standard linear regression method that ignores censoring. The grouped linear regression method is of equivalent power to both the Cox and Weibull proportional hazards methods and is significantly better than the standard linear regression method when censored observations are present. The method is also robust to the proportion of censored individuals and the underlying distribution of the trait. Based on linear regression methodology, the grouped linear regression model is computationally simple and fast and can be readily implemented in freely available statistical software.

Key Words: Age at Onset, Inbred lines, QTL mapping, Survival Analysis, Time to event