Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity

Alexis C. Edwards, Joseph D. Deak, Ian R. Gizer, Dongbing Lai, Chris Chatzinakos, Kirk P. Wilhelmsen, Jonathan Lindsay, Jon Heron, Matthew Hickman, Bradley T. Webb, Silviu Alin Bacanu, Tatiana Foroud, Kenneth S. Kendler, Danielle M. Dick, Marc A. Schuckit

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 h2 SNP = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683, h2 SNP = 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.

Original languageEnglish (US)
JournalAlcoholism: Clinical and Experimental Research
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Meta-Analysis
Genes
Alcohols
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
Hormones
Clocks
Genome-Wide Association Study
Alcohol Drinking
Molecular Biology
Genome
Tissue
Population
Testing

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Edwards, A. C., Deak, J. D., Gizer, I. R., Lai, D., Chatzinakos, C., Wilhelmsen, K. P., ... Schuckit, M. A. (Accepted/In press). Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. Alcoholism: Clinical and Experimental Research. https://doi.org/10.1111/acer.13896

Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. / Edwards, Alexis C.; Deak, Joseph D.; Gizer, Ian R.; Lai, Dongbing; Chatzinakos, Chris; Wilhelmsen, Kirk P.; Lindsay, Jonathan; Heron, Jon; Hickman, Matthew; Webb, Bradley T.; Bacanu, Silviu Alin; Foroud, Tatiana; Kendler, Kenneth S.; Dick, Danielle M.; Schuckit, Marc A.

In: Alcoholism: Clinical and Experimental Research, 01.01.2018.

Research output: Contribution to journalArticle

Edwards, AC, Deak, JD, Gizer, IR, Lai, D, Chatzinakos, C, Wilhelmsen, KP, Lindsay, J, Heron, J, Hickman, M, Webb, BT, Bacanu, SA, Foroud, T, Kendler, KS, Dick, DM & Schuckit, MA 2018, 'Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity', Alcoholism: Clinical and Experimental Research. https://doi.org/10.1111/acer.13896
Edwards, Alexis C. ; Deak, Joseph D. ; Gizer, Ian R. ; Lai, Dongbing ; Chatzinakos, Chris ; Wilhelmsen, Kirk P. ; Lindsay, Jonathan ; Heron, Jon ; Hickman, Matthew ; Webb, Bradley T. ; Bacanu, Silviu Alin ; Foroud, Tatiana ; Kendler, Kenneth S. ; Dick, Danielle M. ; Schuckit, Marc A. / Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. In: Alcoholism: Clinical and Experimental Research. 2018.
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AU - Edwards, Alexis C.

AU - Deak, Joseph D.

AU - Gizer, Ian R.

AU - Lai, Dongbing

AU - Chatzinakos, Chris

AU - Wilhelmsen, Kirk P.

AU - Lindsay, Jonathan

AU - Heron, Jon

AU - Hickman, Matthew

AU - Webb, Bradley T.

AU - Bacanu, Silviu Alin

AU - Foroud, Tatiana

AU - Kendler, Kenneth S.

AU - Dick, Danielle M.

AU - Schuckit, Marc A.

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N2 - 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 h2 SNP = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683, h2 SNP = 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.

AB - 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 h2 SNP = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683, h2 SNP = 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.

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KW - Self-Rating of the Effects of Alcohol

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