Evidence for a Locus on Chromosome 1 That Influences Vulnerability to Alcoholism and Affective Disorder

Abstract

The results suggest that a gene or genes on chromosome 1 may predispose some individuals to alcoholism and others to depression (which may be alcohol induced). Loci on other chromosomes may also be of interest.

A genome wide search for alcoholism susceptibility genes

“…A second region which includes markers D1S196 and D1S2878 is within 1 cM of the gene for an aldehyde dehydrogenase (ALDH9), an enzyme that catalyzes gamma aminobutylaldehyde to GABA. The region near D1S230 has previously been reported by the COGA group to give evidence for linkage Foroud et al, 2000;Nurnberger et al, 2001;Dick et al, 2002]. In the present study, multipoint linkage analysis showed a LOD value of 3.46 (P = 0.002) for marker D1S196 [181.49 cM Marshfield] and a similar LOD value (3.45) at the adjacent marker D1S2878 using a three covariate model that included age, gender, and constraint.…”

“…Reanalysis of the region containing D1S1588 by COGA investigators [Nurnberger et al, 2001;Dick et al, 2002] supported the earlier findings of Reich et al [1998] and Foroud et al [2000]. Nurnberger et al [2001] using phenotypes that included, alternatively, alcoholism with comorbid depression, or alcoholism or depression alone obtained LOD scores of 5.12, 1.52, and 4.66 at marker D1S1588 in initial, replication, and combined data sets, respectively.…”

“…Nurnberger et al [2001] using phenotypes that included, alternatively, alcoholism with comorbid depression, or alcoholism or depression alone obtained LOD scores of 5.12, 1.52, and 4.66 at marker D1S1588 in initial, replication, and combined data sets, respectively. Dick et al [2002] using a derived phenotype based on a principal component analysis of DSM-IIIR items and scales from the Tridimensional Personality Questionnaire (TPQ) reported evidence for linkage (LOD = 3.3) to a region that included marker D1S518.…”

“…One of the ways this has been handled in genetic studies is to vary the "bandwidth" of the phenotype, observing changes in the evidence for linkage as one decreases or increases the breadth of the phenotype. One example of how this strategy can be beneficial in finding pleiotropic effects of genetic loci comes from the report by Nurnberger et al [2001] in which evidence for a locus on chromosome 1 that influences both alcoholism and affective disorder was found using a variable width phenotype.…”

Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans

“…The human CNR2 gene is located on chromosomes 1p36, nearby where only one report has indicated a broad and weak linkage to alcoholism, 31 although common linkage area was reported around chromosome 1p31, not very close to CNR2 locus. 32 Because our genetics data indicated that CNR2 has a moderate effect on human alcoholism and our mouse studies revealed the contributions of non genetic factors related to development of alcohol preference, it is likely that reinforcement of alcohol preference/addiction and stress may also influence endocannabinoids regulation that alters Cnr2 gene/protein expression in CNS. It is also likely that CNR2 contributes to initiation and development of alcoholism during periods of vulnerability owing to stress.…”