A cis-eQTL in OPRM1 is Associated with Subjective Response to Alcohol and Alcohol Use.

paper Cited Public

Authors: Otto, Jacqueline M; Gizer, Ian R; Deak, Joseph D; Fleming, Kimberly A; Bartholow, Bruce D
Year: 2017
Journal: Alcoholism, clinical and experimental research
PMID: 28273335
DOI: 10.1111/acer.13369
PMCID: PMC5404990

BACKGROUND: A functional polymorphism within the μ-opioid receptor (OPRM1) 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 OPRM1, 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 OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 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 OPRM1, subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.

#	Section	Preview
0	Introduction	Genetic factors are one of numerous components thought to contribute to the development of substance…
1	Introduction	and unpleasant effects, and tension reduction (Ray et al., 2009; Bujarski et al., 2015). Variability…
2	Introduction	Alcohol’s mechanism of action includes its effects on the brain’s “reward centers” in the…
3	Introduction	2012). Though findings from in vitro studies have been mixed (for a review, see Ray et al., 2012),…
4	Introduction	Given the potential functional relevance of rs1799971 to mu-opioid receptor activity, numerous…
5	Introduction	of influence conferred by rs1799971 (Arias et al., 2006; Chen et al., 2012; Schwantes-An et al.,…
6	Introduction	To provide a fuller examination of OPRM1 variation in relation to substance use phenotypes, a recent…
7	Introduction	The current study sought to test this hypothesis, and in this way, extend the findings from (Hancock…
8	Materials and Methods — Sample	Participants were individuals with both genotype data (i.e., saliva samples suitable for DNA…
9	Materials and Methods — Sample	down on drinking; prescription medication other than oral contraception; pregnancy) or that would…
10	Materials and Methods — Self-report Measures — Self-Rating of the Effects of Alcohol (SRE) form	The 12-item SRE (Schuckit et al., 1997) was used to assess level of response to alcohol. The SRE…
11	Materials and Methods — Self-report Measures — Self-Rating of the Effects of Alcohol (SRE) form	Given that an item can be included in the score only if the participant reports having experienced…
12	Materials and Methods — Self-report Measures — Self-Rating of the Effects of Alcohol (SRE) form	person-mean imputation in which item responses are converted to z-scores before averaging across…
13	Materials and Methods — Self-report Measures — Alcohol Sensitivity Questionnaire (ASQ)	The 15-item ASQ (O’Neill et al., 2002) was also used to assess level of response to alcohol, and…
14	Materials and Methods — Self-report Measures — Alcohol use	Using items adapted from the NIAAA Task Force recommendations (NIAAA, 2003), participants estimated…
15	Materials and Methods — Subjective Effects of Alcohol — Subjective intoxication	The alcohol challenge portion of the study included periodic assessments during which participants…
16	Materials and Methods — Subjective Effects of Alcohol — Stimulation and sedation	Ratings of participants’ feelings of stimulation and sedation during the alcohol challenge portion…
17	Materials and Methods — Procedure	Participants attended a preliminary laboratory session during which they completed all retrospective…
18	Materials and Methods — Procedure	A five-minute absorption period followed beverage administration, and participants then completed…
19	Materials and Methods — Genotyping	As noted, this study was part of a larger effort examining genetic influences on cognition, and…

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In this knowledge base

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