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Genetic Variants in the Fat Mass- and Obesity-Associated (FTO) Gene are Associated with Alcohol Dependence

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Abstract

Variants (such as rs9939609) in the fat mass- and obesity-associated (FTO) gene have been associated with obesity, type 2 diabetes, some cancers, and alcohol consumption. This study tested the associations of 167 single-nucleotide polymorphisms (SNPs) within FTO gene with alcohol dependence (AD) using two Caucasian samples: the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis of AD as a binary trait was performed using the PLINK software. For the SAGE sample, the top three SNPs showing associations with AD were rs8062891, rs1108086, and rs1420318 (p = 0.00088, 0.00086 and 0.00086, respectively). Two SNPs (rs12597786 and rs7204609) associated with AD in the SAGE sample (p = 0.017 and 0.034, respectively) were replicated in the COGA sample (p = 0.017 and 0.014, respectively). Through meta-analysis of two samples using PLINK, the top three SNPs associated with AD were rs8062891, rs12597786, and rs7204609 (p = 0.00064, 0.00076 and 0.0011, respectively). Haplotype analysis in the SAGE sample further supported the associations with AD in single-marker analysis. In addition, we found association of rs17817449 (which has a strong linkage disequilibrium with rs9939609) with AD in the SAGE sample (p = 0.00339). The findings provide evidence of joint intervention and prevention of AD and obesity.

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Acknowledgments

Funding support for the (CIDR-COGA Study) was provided through the Center for Inherited Disease Research (CIDR) and the Collaborative Study on the Genetics of Alcoholism (COGA). The CIDR–COGA Study is a genome-wide association studies funded as part of the COGA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the COGA. Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the COGA (U10 AA008401). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?Db = gap through dbGaP accession number: phs000125.v1.p1. Funding support for the SAGE was provided through the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) grant U01 HG004422. SAGE is one of the GWAS funded as part of the GENEVA under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (grant U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by COGA (grant U10 AA008401), COGEND (grant P01 CA089392), and FSCD (grant R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by NIH GEI grant U01HG004438, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/ study.cgi study_id = phs000092.v1.p1 through dbGaP accession number phs000092.v1.p.1. This study was approved by the Internal Review Board (IRB), East Tennessee State University.

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Authors and Affiliations

  1. Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, Johnson City, TN, PO Box 70259, 37614-1700, USA

    Liang Wang, Xuefeng Liu, Min Zeng & Ke-Sheng Wang

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Xingguang Luo & Lingjun Zuo

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  1. Liang Wang
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Correspondence to Ke-Sheng Wang.

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Wang, L., Liu, X., Luo, X. et al. Genetic Variants in the Fat Mass- and Obesity-Associated (FTO) Gene are Associated with Alcohol Dependence. J Mol Neurosci 51, 416–424 (2013). https://doi.org/10.1007/s12031-013-0044-2

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