@article{a76255700f7b4a5da0cc1513b7ed2b0a,
title = "Genome-wide association studies of maximum number of drinks",
abstract = "Maximum number of drinks (MaxDrinks) defined as {"}Maximum number of alcoholic drinks consumed in a 24-h period{"} is an intermediate phenotype that is closely related to alcohol dependence (AD). Family, twin and adoption studies have shown that the heritability of MaxDrinks is approximately 0.5. We conducted the first genome-wide association (GWA) study and meta-analysis of MaxDrinks as a continuous phenotype. 1059 individuals were from the Collaborative Study on the Genetics of Alcoholism (COGA) sample and 1628 individuals were from the Study of Addiction - Genetics and Environment (SAGE) sample. Family sample with 3137 individuals was from the Australian twin-family study of alcohol use disorder (OZALC). Two population-based Caucasian samples (COGA and SAGE) with 1 million single-nucleotide polymorphisms (SNPs) were used for gene discovery and one family-based Caucasian sample was used for replication. Through meta-analysis we identified 162 SNPs associated with MaxDirnks (p<10-4). The most significant association with MaxDrinks was observed with SNP rs11128951 (p=4.27×10-8) near SGOL1 gene at 3p24.3. Furthermore, several SNPs (rs17144687 near DTWD2, rs12108602 near NDST4, and rs2128158 in KCNB2) showed significant associations with MaxDrinks (p<5×10-7) in the meta-analysis. Especially, 8 SNPs in DDC gene showed significant associations with MaxDrinks (p<5×10-7) in the SAGE sample. Several flanking SNPs in above genes/regions were confirmed in the OZALC family sample. In conclusions, we identified several genes/regions associated with MaxDrinks. These findings can improve the understanding about the pathogenesis of alcohol consumption phenotypes and alcohol-related disorders.",
keywords = "DDC, DTWD2, Genome-wide association, KCNB2, Maximum number of drinks, Meta-analysis, NDST4, SGOL1",
author = "Yue Pan and Xingguang Luo and Xuefeng Liu and Wu, {Long Yang} and Qunyuan Zhang and Liang Wang and Weize Wang and Lingjun Zuo and Wang, {Ke Sheng}",
note = "Funding Information: The dataset for replication study was obtained from the CIDA database found at http://www.ncbi.nlm.nih.gov/projects/gap/ through the dbGAP accession number Study Accession: phs000181.v1.p1. Funding support for the CIDR-OZALC GWAS was provided through the Center for Inherited Disease Research (CIDR) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). CIDR-OZALC GWAS is a genome-wide association studies funded as part of the NIAAA grant 5 R01 AA013320-04. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the CIDR-OZALC GWAS. Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the MARC: Risk Mechanisms in Alcoholism and Comorbidity (MARC; P60 AA011998-11). 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/projects/gap/cgibin/study.cgistudy_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p.1. Funding Information: Funding support for the CIDR–COGA Study was provided through the 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 Collaborative Study on the Genetics of Alcoholism (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 were provided by the Collaborative Study on the Genetics of Alcoholism (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 Information: 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.cgistudy_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p.1. Funding Information: This work was partially supported by RDC major research grant (to KSW and XFL), East Tennessee State University. This work was supported in part by K01 DA029643, R21 AA020319, R21 AA021380, NARSAD, and ABMRF (to Luo X and Zuo L). Funding agency had no further role in study design; in the analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. ",
year = "2013",
month = nov,
doi = "10.1016/j.jpsychires.2013.07.013",
language = "English (US)",
volume = "47",
pages = "1717--1724",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier Limited",
number = "11",
}
