Genome search for alcohol dependence using the weighted pairwise correlation linkage method: interesting findings on chromosome 4

The nonparametric (model-free) method of linkage analysis Weighted Pairwise Correlation (WPC) has been proposed by Commenges [1994], and extended to incorporate identity-by-descent (IBD) information [Zinn-Justin and Abel, 1999]. We performed an autosome-wide scan in the Collaborative Study on the Genetics of Alcoholism data using the WPC-IBD method, considering two phenotypes related to alcohol dependence defined as residuals of binary traits adjusted for age and sex. Three chromosome 4 markers located in a region of 50 cM spanning from GABRB1 to D4S1651 provided Monte Carlo (MC) p-values lower than 0.005, confirming the possible influence of beta 1 GABA receptor and ADH genes in alcoholism. Furthermore, marker D15S642, not far from the ALDH6 gene, provided an MC p-value of 0.0005 in ethnic groups "White, Hispanic" and "White, non-Hispanic."