Premium
A cis‐ eQTL in OPRM 1 is Associated with Subjective Response to Alcohol and Alcohol Use
Author(s) -
Otto Jacqueline M.,
Gizer Ian R.,
Deak Joseph D.,
Fleming Kimberly A.,
Bartholow Bruce D.
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13369
Subject(s) - alcohol , allele , medicine , alcohol dependence , psychology , genetics , biology , gene , biochemistry
Background A functional polymorphism within the μ ‐opioid receptor ( OPRM 1 ) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM 1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150‐C allele is associated with decreased OPRM 1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM 1 that increases risk for a variety of alcohol use phenotypes. Methods Participants with genotype and phenotype data from a larger experimental study ( N = 152) were assessed on measures of subjective response to alcohol and alcohol use. Measures included (i) the Self‐Rating of the Effects of Alcohol and the Alcohol Sensitivity Questionnaire, (ii) the Biphasic Alcohol Effects Scale ( BAES ) and ratings of subjective intoxication, and (iii) average number of drinks per week in the past month. Results Compared to rs3778150‐T homozygous individuals, carriers of the rs3778150‐C allele exhibited significantly lower retrospective self‐report levels of alcohol sensitivity. Carriers of the rs3778150‐C allele also exhibited lower levels of BAES alcohol‐related stimulation during an alcohol challenge and reported higher levels of drinking in the last 30 days. With the exception of lower levels of BAES alcohol‐related sedation, the rs1799971 variant did not show consistent significant association with any of the alcohol phenotypes in the presence of rs3778150. Conclusions Results suggest that rs3778150 may be causally related to alcohol use phenotypes, and could potentially account for previously observed associations of rs1799971 with substance use phenotypes. Future studies may investigate potential causal relations among genetic variants in OPRM 1 , subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.