A genome-wide search for genes that relate to a low level of response to alcohol

Background: The low level of response (LR) to alcohol is genetically influe nced in both humans and animals, and a low LR is a characteristic of offspr ing of alcoholics that has been reported to predict alcoholism 10 and 15 ye ars later. The genes that contribute to a low LR have not yet been identifi ed. Methods: A 12-item questionnaire that measures LR, the Self Rating of the E ffects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genet ic material was available. These subjects were genotyped by using 336 marke rs with an average heterozygosity of 0.74 and an average intermarker distan ce of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair an alyses were carried out for the SRE measure related to early drinking exper iences. Results: Correlations of SRE scores across related individuals were signifi cant and between 0.16 and 0.22 for most values, compared with nonsignifican t correlations of 0.03 or less among unrelated individuals. Linkage analyse s performed by using the FIRST 5 variables (first five times alcohol is con sumed) identified four chromosomal regions with lod scores greater than or equal to2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. Conclusions: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.