TY - JOUR
T1 - Genome-wide association study of alcohol dependence implicates a region on chromosome 11
AU - Edenberg, Howard J.
AU - Koller, Daniel L.
AU - Xuei, Xiaoling
AU - Wetherill, Leah
AU - McClintick, Jeanette N.
AU - Almasy, Laura
AU - Bierut, Laura J.
AU - Bucholz, Kathleen K.
AU - Goate, Alison
AU - Aliev, Fazil
AU - Dick, Danielle
AU - Hesselbrock, Victor
AU - Hinrichs, Anthony
AU - Kramer, John
AU - Kuperman, Sam
AU - Nurnberger, John I.
AU - Rice, John P.
AU - Schuckit, Marc A.
AU - Taylor, Robert
AU - Todd Webb, B.
AU - Tischfield, Jay A.
AU - Porjesz, Bernice
AU - Foroud, Tatiana
PY - 2010/5
Y1 - 2010/5
N2 - Background: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. Methods: We carried out a genome-wide association study (GWAS) on a case-control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p ≤ 2.1 × 10-4) in a sample of alcohol-dependent families and performed pedigree-based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. Results: Although no single SNP met genome-wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case-control study, the follow-up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3. Conclusions: We have identified several promising associations that warrant further examination in independent samples.
AB - Background: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. Methods: We carried out a genome-wide association study (GWAS) on a case-control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p ≤ 2.1 × 10-4) in a sample of alcohol-dependent families and performed pedigree-based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. Results: Although no single SNP met genome-wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case-control study, the follow-up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3. Conclusions: We have identified several promising associations that warrant further examination in independent samples.
KW - Alcohol Dependence
KW - Case-Control Study
KW - Family Study
KW - Gene Expression
KW - Genome-Wide Association Study
UR - http://www.scopus.com/inward/record.url?scp=77951557173&partnerID=8YFLogxK
U2 - 10.1111/j.1530-0277.2010.01156.x
DO - 10.1111/j.1530-0277.2010.01156.x
M3 - Article
C2 - 20201924
AN - SCOPUS:77951557173
SN - 0145-6008
VL - 34
SP - 840
EP - 852
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 5
ER -