Sib-pair linkage analysis of alcohol dependence taking into account covariates and age-of-onset variability: evaluation of the residual approach.

The construction of residuals allowed us to consider a phenotype related to alcohol dependence (ALDX1) adjusted for age, gender and current smoking status. Using the Haseman and Elston regression test, we compared genome scan results for detection of loci for the unadjusted and adjusted ALDX1 phenotypes in the Collaborative Study on the Genetics of Alcoholism (COGA) data. More markers were significant at the 1% level for the binary than for the residual analyses. Overall, our residual analyses do not show substantial improvement in their ability to detect linkage for alcohol dependence in the COGA data. This may be due to the relatively small sample size of discordant sib pairs.