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ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.

ABSTRACT: Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology.A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans.Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51 × 10(-8)). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption.The evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.

SUBMITTER: Chen XD

PROVIDER: S-EPMC4174677 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.

Chen Xiang-ding XD Xiong Dong-hai DH Yang Tie-lin TL Pei Yu-fang YF Guo Yan-fang YF Li Jian J Yang Fang F Pan Feng F Tan Li-jun LJ Yan Han H Liu Xiao-gang XG Lei Shu-feng SF Li Xi X Ning Ling-ling LL Zhu Xue-zhen XZ Levy Shawn S Kranzler Henry R HR Farrer Lindsay A LA Gelernter Joel J Recker Robert R RR Deng Hong-wen HW

Chinese medical journal 20120301 6

<h4>Background</h4>Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes u ...[more]

PMID: 22613542

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Project description:Alcohol is the most common drug among youth and a major contributor to morbidity and mortality worldwide. Billions of dollars are spent annually marketing alcohol.To examine the reach of television alcohol advertising and its effect on drinking among underage youth.Longitudinal telephone- and web-based surveys conducted in 2011 and 2013 involving 2541 US adolescents 15 to 23 years of age at baseline, with 1596 of these adolescents completing the follow-up survey. Cued recall of television advertising images for top beer and distilled spirits brands that aired nationally in 2010-2011 (n = 351). Images were digitally edited to remove branding, and the respondents were queried about 20 randomly selected images. An alcohol advertising receptivity score was derived (1 point each for having seen the ad and for liking it, and 2 points for correct brand identification). Fast-food ads that aired nationally in 2010-2011 (n = 535) were similarly queried to evaluate message specificity.Among the underage youth at baseline, we determined (1) the onset of drinking among those who never drank, (2) the onset of binge drinking among those who were never binge drinkers, and (3) the onset of hazardous drinking among those with an Alcohol Use Disorders Identification Test consumption subscore of less than 4. Multivariate regressions were used to predict each outcome, controlling for covariates (demographics, drinking among friends and parents, and sensation seeking), weighting to the US population, and using multiple imputation to address loss to follow-up.Underage participants were only slightly less likely than participants of legal drinking age to have seen alcohol ads (the mean percentage of ads seen were 23.4%, 22.7%, and 25.6%, respectively, for youth 15-17, 18-20, and 21-23 years of age; P <?.005). The transition to binge and hazardous drinking occurred for 29% and 18% of youth 15 to 17 years of age and for 29% and 19% of youth 18 to 20 years years of age, respectively. Among underage participants, the alcohol advertising receptivity score independently predicted the onset of drinking (adjusted odds ratio [AOR], 1.69 [95% CI, 1.17-2.44]), the onset of binge drinking (AOR, 1.38 [95% CI, 1.08-1.77]), and the onset of hazardous drinking (AOR, 1.49 [95% CI, 1.19-1.86]). Fast-food advertising receptivity was not associated with any drinking outcome.Receptivity to television alcohol advertising predicted the transition to multiple drinking outcomes. The findings are consistent with the idea that marketing self-regulation has failed to keep television alcohol advertising from reaching large numbers of underage persons and affecting their drinking patterns.

Dataset Information

ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.

Publications

ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.

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