Format

Send to

Choose Destination
Alcohol Clin Exp Res. 2018 Dec;42(12):2349-2359. doi: 10.1111/acer.13896. Epub 2018 Oct 28.

Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity.

Author information

1
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
2
Department of Psychological Sciences, University of Missouri, Columbia, Missouri.
3
Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana.
4
Departments of Neurology and Genetics, University of North Carolina, Chapel Hill, North Carolina.
5
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia.
6
Population Health Sciences, University of Bristol, Bristol, UK.
7
Department of Psychology, Virginia Commonwealth University, Richmond, Virginia.
8
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.
9
College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, Virginia.
10
Department of Psychiatry, University of California, San Diego, La Jolla, California.

Abstract

BACKGROUND:

Previous studies indicate that low initial sensitivity to alcohol may be a risk factor for later alcohol misuse. Evidence suggests that initial sensitivity is influenced by genetic factors, but few molecular genetic studies have been reported.

METHODS:

We conducted a meta-analysis of 2 population-based genome-wide association studies of the Self-Rating of the Effects of Alcohol scale. Our final sample consisted of 7,339 individuals (82.3% of European descent; 59.2% female) who reported having used alcohol at least 5 times. In addition, we estimated single nucleotide polymorphism (SNP)-based heritability and conducted a series of secondary aggregate genetic analyses.

RESULTS:

No individual locus reached genome-wide significance. Gene and set based analyses, both overall and using tissue-specific expression data, yielded largely null results, and genes previously implicated in alcohol problems and consumption were overall not associated with initial sensitivity. Only 1 gene set, related to hormone signaling and including core clock genes, survived correction for multiple testing. A meta-analysis of SNP-based heritability resulted in a modest estimate of h SNP 2  = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683, h SNP 2  = 0.36, SE = 0.14, p = 0.04). No significant genetic correlations with other relevant outcomes were observed.

CONCLUSIONS:

Findings yielded only modest support for a genetic component underlying initial alcohol sensitivity. Results suggest that its biological underpinnings may diverge somewhat from that of other alcohol outcomes and may be related to core clock genes or other aspects of hormone signaling. Larger samples, ideally of prospectively assessed samples, are likely necessary to improve gene identification efforts and confirm the current findings.

KEYWORDS:

Avon Longitudinal Study of Parents and Children; Genetics; Genome-Wide Association Studies; Heritability; Initial Alcohol Sensitivity; Self-Rating of the Effects of Alcohol

PMID:
30276832
PMCID:
PMC6286211
[Available on 2019-12-01]
DOI:
10.1111/acer.13896
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley Icon for eScholarship, California Digital Library, University of California
Loading ...
Support Center