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

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

Research output: Contribution to journalArticle

224 Citations (Scopus)

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 2010

Fingerprint

Chromosomes, Human, Pair 11
Genome-Wide Association Study
Chromosomes
Alcoholism
Single Nucleotide Polymorphism
Genes
Alcohols
Polymorphism
Nucleotides
Street Drugs
Pedigree
Multigene Family
Diagnostic and Statistical Manual of Mental Disorders
Case-Control Studies
Ethanol
Genome
Gene expression
Gene Expression
Brain
Railroad cars

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Genome-wide association study of alcohol dependence implicates a region on chromosome 11. / Edenberg, Howard; Koller, Daniel L.; Xuei, Xiaoling; Wetherill, Leah; McClintick, Jeanette; Almasy, Laura; Bierut, Laura J.; Bucholz, Kathleen K.; Goate, Alison; Aliev, Fazil; Dick, Danielle; Hesselbrock, Victor; Hinrichs, Anthony; Kramer, John; Kuperman, Sam; Nurnberger, John; Rice, John P.; Schuckit, Marc A.; Taylor, Robert; Todd Webb, B.; Tischfield, Jay A.; Porjesz, Bernice; Foroud, Tatiana.

In: Alcoholism: Clinical and Experimental Research, Vol. 34, No. 5, 05.2010, p. 840-852.

Research output: Contribution to journalArticle

Edenberg, H, Koller, DL, Xuei, X, Wetherill, L, McClintick, J, Almasy, L, Bierut, LJ, Bucholz, KK, Goate, A, Aliev, F, Dick, D, Hesselbrock, V, Hinrichs, A, Kramer, J, Kuperman, S, Nurnberger, J, Rice, JP, Schuckit, MA, Taylor, R, Todd Webb, B, Tischfield, JA, Porjesz, B & Foroud, T 2010, 'Genome-wide association study of alcohol dependence implicates a region on chromosome 11', Alcoholism: Clinical and Experimental Research, vol. 34, no. 5, pp. 840-852. https://doi.org/10.1111/j.1530-0277.2010.01156.x
Edenberg, Howard ; Koller, Daniel L. ; Xuei, Xiaoling ; Wetherill, Leah ; McClintick, Jeanette ; Almasy, Laura ; Bierut, Laura J. ; Bucholz, Kathleen K. ; Goate, Alison ; Aliev, Fazil ; Dick, Danielle ; Hesselbrock, Victor ; Hinrichs, Anthony ; Kramer, John ; Kuperman, Sam ; Nurnberger, John ; Rice, John P. ; Schuckit, Marc A. ; Taylor, Robert ; Todd Webb, B. ; Tischfield, Jay A. ; Porjesz, Bernice ; Foroud, Tatiana. / Genome-wide association study of alcohol dependence implicates a region on chromosome 11. In: Alcoholism: Clinical and Experimental Research. 2010 ; Vol. 34, No. 5. pp. 840-852.
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AU - Koller, Daniel L.

AU - Xuei, Xiaoling

AU - Wetherill, Leah

AU - McClintick, Jeanette

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

AU - Rice, John P.

AU - Schuckit, Marc A.

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AU - Foroud, Tatiana

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