A genome screen of maximum number of drinks as an alcoholism phenotype

Abstract

The Collaborative Study on the Genetics of Alcoholism (COGA) is a multicenter research program to detect and map susceptibility genes for alcohol dependence and related phenotypes. The measure M of "maximum number of drinks consumed in a 24-hour period" is closely related to alcoholism diagnosis in this dataset and provides a quantitative measure to grade nonalcoholic individuals. Twin studies have shown log(M) to have a heritability of approximately 50%. Genome screens for this trait were performed in two distinct genotyped samples (wave 1 and wave 2), and in the combined sample. MAPMAKER/SIBS was used to carry out Haseman-Elston based regression analyses. On chromosome 4, an unweighted all-pairs multipoint LOD of 2.2 was obtained between D4S2407 and D4S1628 in wave 1; in wave 2, the region flanked by D4S2404 and D4S2407 gave a LOD of 1.5. In the combined sample, the maximal LOD was 3.5 very close to D4S2407. This evidence for linkage is in the region of the alcohol dehydrogenase gene cluster on chromosome 4. These findings on chromosome 4 are consistent with a prior report from COGA in which strictly defined nonalcoholic subjects in wave 1 were analyzed. The present analysis on log(M) allows more individuals to be included and thus is potentially more powerful.

Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample

“…It is also worth noting that some linkage peaks previously identified in COGA on chromosome 4 and 7 (Saccone et al, 2000;Saccone et al, 2005;Foroud et al, 2000;Reich et al, 1998;Nurnberger, Jr. et al, 2001) were not identified in the current study. Those peaks harbor genes such as GABRA2, ADH (on chromosome 4) and CHRM2 and hTAS2R16 (on chromosome 7), which have subsequently found to be associated with risk for alcoholism Wang et al, 2004;Edenberg et al, 2006a;Hinrichs et al, 2006).…”

Genome-wide linkage scan for nicotine dependence in European Americans and its converging results with African Americans in the Mid-South Tobacco Family sample

“…The positive region for ND on chromosome 2 has been linked to alcohol dependence in the COGA sample 38,39 and in the Oregon Smoking Families study. 40 The linkage region for ND on chromosome 4 detected in the EA sample of the MSTF cohort has also been linked to alcohol dependence in three independent samples 35,38,40,41 and to polysubstance abuse. 36,37 Moreover, two recent large-scale association studies also provide partial support to some of our linkage findings.…”

α-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats

“…Polymorphisms in several of the genes in this gene cluster are clearly associated with a decreased risk of alcoholism (41,42). This region also displays linkage to an alcohol-related phenotype, the maximum number of drinks consumed in a 24-h period (43). It will be interesting to determine whether variation in the human ␣-synuclein gene is associated with an alcohol-related phenotype.…”