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A candidate gene association study of alcohol consumption in young women.

ABSTRACT: Excessive alcohol consumption contributes to significant morbidity and mortality. Heritable influences contribute to 50% of the variation in alcohol consumption, suggesting the important role of genes. We used data on a previously defined alcohol consumption factor score in a sample of 827 young women to investigate association with 1,014 single-nucleotide polymorphisms in genes related to addiction.Data were drawn from the Missouri Adolescent Female Twin Study (MOAFTS) with replication in the college drinking sample (CDS). Genotypic and phenotypic data were available on 827 MOAFTS and 100 CDS women of European-American ancestry. Data on 1,014 single-nucleotide polymorphisms (SNPs) across 130 genes related to addiction were utilized. Association was conducted in QTDT, which allows for identity-by-descent information to account accurately for twin status in the analysis. The total association variance components model was used, with specification of variance components for relatedness in MOAFTS.The top signals included clusters of SNPs in tryptophan hydroxylase 2 (TPH2) (e.g., rs1386496, p = 0.0003) and dopa decarboxylase (DDC) (e.g., rs3779084, p = 0.0008), genes that encode proteins responsible for serotonin synthesis. Additional polymorphisms in ADH1B, ADH1C, ADH7, and ADH1A1 were also associated at p < 0.05. The false discovery rate for the top signal (p = 0.0003) was 0.15, suggesting nominal significance only. Replication was limited and noted for 2 SNPs in ADH1C.While no results survive the burden of multiple testing, nominal findings in TPH2 and DDC suggest the potential role of the serotonin synthesis pathway in alcohol consumption.

SUBMITTER: Agrawal A

PROVIDER: S-EPMC3239405 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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A candidate gene association study of alcohol consumption in young women.

Agrawal Arpana A Lynskey Michael T MT Todorov Alexandre A AA Schrage Andrew J AJ Littlefield Andrew K AK Grant Julia D JD Zhu Qin Q Nelson Elliot C EC Madden Pamela A F PA Bucholz Kathleen K KK Sher Kenneth J KJ Heath Andrew C AC

Alcoholism, clinical and experimental research 20101208 3

<h4>Background</h4>Excessive alcohol consumption contributes to significant morbidity and mortality. Heritable influences contribute to 50% of the variation in alcohol consumption, suggesting the important role of genes. We used data on a previously defined alcohol consumption factor score in a sample of 827 young women to investigate association with 1,014 single-nucleotide polymorphisms in genes related to addiction.<h4>Methods</h4>Data were drawn from the Missouri Adolescent Female Twin Study ...[more]

PMID: 21143251

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Project description:BackgroundThe role of alcohol use in the development of depression is unclear. We aimed to investigate whether alcohol dependence, but not high frequency or quantity of consumption, during adolescence increased the risk of depression in young adulthood.MethodsIn this prospective cohort study, we included adolescents who were born to women recruited to the Avon Longitudinal Study of Parents and Children in Avon, UK, with delivery dates between April 1, 1991, and Dec 31, 1992. Alcohol dependence and consumption were measured at about age 16 years, 18 years, 19 years, 21 years, and 23 years using the self-reported Alcohol Use Disorders Identification Test, and at about age 18 years, 21 years, and 23 years using items corresponding to DSM-IV symptoms. The primary outcome was depression at age 24 years, assessed using the Clinical Interview Schedule Revised. Analyses were probit regressions between growth factors for alcohol dependence and consumption and depression, before and after adjustments for confounders: sex, housing tenure, maternal education, maternal depressive symptoms, parents' alcohol use, conduct problems at age 4 years, being bullied from age 12-16 years, and frequency of smoking cigarettes or cannabis. Adolescents were included in analyses if they had data from at least one timepoint for alcohol use and confounders.FindingsWe included 3902 adolescents (2264 [58·0%] female; 1638 [42·0%] male) in our analysis, and 3727 (96·7%) of 3853 participants with data on ethnicity were White. After adjustments, we found a positive association between alcohol dependence at 18 years of age (latent intercept) and depression at 24 years of age (probit coefficient 0·13 [95% CI 0·02 to 0·25]; p=0·019), but no association between rate of change (linear slope) and depression (0·10 [-0·82 to 1·01]; p=0·84). There was no evidence of an association between alcohol consumption and depression (latent intercept probit coefficient -0·01 [-0·06 to 0·03]; p=0·60; linear slope 0·01 [-0·40 to 0·42]; p=0·96) after adjustments.InterpretationPsychosocial or behavioural interventions that reduce the risk of alcohol dependence during adolescence could contribute to preventing depression in young adulthood.FundingUK Medical Research Council and Alcohol Research UK (grant number MR/L022206/1).

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A candidate gene association study of alcohol consumption in young women.

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A candidate gene association study of alcohol consumption in young women.

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