Genome-wide association study of alcohol dependence implicates a region on chromosome 11

Howard J. Edenberg, Daniel L. Koller, Xiaoling Xuei, Leah Wetherill, Jeanette N. McClintick, Laura Almasy, Laura J. Bierut, Kathleen K. Bucholz, Alison Goate, Fazil Aliev, Danielle Dick, Victor Hesselbrock, Anthony Hinrichs, John Kramer, Sam Kuperman, John I. Nurnberger, John P. Rice, Marc A. Schuckit, Robert Taylor, B. Todd WebbJay A. Tischfield, Bernice Porjesz, Tatiana Foroud

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)840-852
Number of pages13
JournalAlcoholism: Clinical and Experimental Research
Volume34
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • Alcohol Dependence
  • Case-Control Study
  • Family Study
  • Gene Expression
  • Genome-Wide Association Study

Fingerprint Dive into the research topics of 'Genome-wide association study of alcohol dependence implicates a region on chromosome 11'. Together they form a unique fingerprint.

  • Cite this

    Edenberg, H. J., Koller, D. L., Xuei, X., Wetherill, L., McClintick, J. N., Almasy, L., Bierut, L. J., Bucholz, K. K., Goate, A., Aliev, F., Dick, D., Hesselbrock, V., Hinrichs, A., Kramer, J., Kuperman, S., Nurnberger, J. I., Rice, J. P., Schuckit, M. A., Taylor, R., ... Foroud, T. (2010). Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcoholism: Clinical and Experimental Research, 34(5), 840-852. https://doi.org/10.1111/j.1530-0277.2010.01156.x