Linkage analysis for diseases with variable age of onset

We present a method for the multivariate linkage analysis of the age of ons et of a disease, The approach allows the incorporation of covariates for th e study of gene by environment interactions. It is applicable to general pe digrees, The likelihood of the data is expressed as a function of the numbe r of alleles identical by descent at a marker, the censored ages of onset a nd disease status, and environmental exposures, In a simulation study, we c ompare the power to detect linkage under different sampling schemes for eit her a dominant or recessive trait when approximately 10% of individuals are gene carriers. The majority of the linkage information from a sample of ra ndomly selected sib pairs was retained when the analyses were limited to si bships with one sibling having early-onset disease (<59 years old), Incorpo rating parental phenotypes could improve the power to detect the gene. When the sample consists of affected sib pairs (ASPs) having variable age of on set, the likelihood ratio (LR) test had higher power than the means (t(2)) test for detecting a locus with a large genetic relative risk (R-g = 20). H owever, the power of the two tests was similar when ASPs are selected so th at the proband has an early onset of disease. Lastly, the LR test had more power than the t(2) test to detect linkage in the presence of gene by envir onment interactions. Copyright (C) 2000 S. Karger AG, Basel.