A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53

J. C. Wang, Tatiana Foroud, A. L. Hinrichs, N. X H Le, S. Bertelsen, J. P. Budde, O. Harari, D. L. Koller, L. Wetherill, A. Agrawal, L. Almasy, A. I. Brooks, K. Bucholz, D. Dick, V. Hesselbrock, E. O. Johnson, S. Kang, M. Kapoor, J. Kramer, S. KupermanP. A F Madden, N. Manz, N. G. Martin, Jeanette McClintick, G. W. Montgomery, John Nurnberger, M. Rangaswamy, J. Rice, M. Schuckit, J. A. Tischfield, J. B. Whitfield, Xiaoling Xuei, B. Porjesz, A. C. Heath, Howard Edenberg, L. J. Bierut, A. M. Goate

Research output: Contribution to journalArticle

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Abstract

Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10 -8, inflation-corrected P=9.4 × 10 -7). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D′=1, r 2 ≥ 0.95), have previously been associated with risk for bipolar disorder.

Original languageEnglish
Pages (from-to)1218-1224
Number of pages7
JournalMolecular Psychiatry
Volume18
Issue number11
DOIs
StatePublished - Nov 2013

Fingerprint

Genome-Wide Association Study
Pedigree
Alcoholism
Diagnostic and Statistical Manual of Mental Disorders
Genes
Single Nucleotide Polymorphism
Alcohols
Endophenotypes
Twin Studies
Economic Inflation
Bipolar Disorder
Phenotype

Keywords

  • C15orf53; DSM-IV alcohol-dependence symptoms
  • Family-based GWAS
  • Quantitative traits

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Wang, J. C., Foroud, T., Hinrichs, A. L., Le, N. X. H., Bertelsen, S., Budde, J. P., ... Goate, A. M. (2013). A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Molecular Psychiatry, 18(11), 1218-1224. https://doi.org/10.1038/mp.2012.143

A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. / Wang, J. C.; Foroud, Tatiana; Hinrichs, A. L.; Le, N. X H; Bertelsen, S.; Budde, J. P.; Harari, O.; Koller, D. L.; Wetherill, L.; Agrawal, A.; Almasy, L.; Brooks, A. I.; Bucholz, K.; Dick, D.; Hesselbrock, V.; Johnson, E. O.; Kang, S.; Kapoor, M.; Kramer, J.; Kuperman, S.; Madden, P. A F; Manz, N.; Martin, N. G.; McClintick, Jeanette; Montgomery, G. W.; Nurnberger, John; Rangaswamy, M.; Rice, J.; Schuckit, M.; Tischfield, J. A.; Whitfield, J. B.; Xuei, Xiaoling; Porjesz, B.; Heath, A. C.; Edenberg, Howard; Bierut, L. J.; Goate, A. M.

In: Molecular Psychiatry, Vol. 18, No. 11, 11.2013, p. 1218-1224.

Research output: Contribution to journalArticle

Wang, JC, Foroud, T, Hinrichs, AL, Le, NXH, Bertelsen, S, Budde, JP, Harari, O, Koller, DL, Wetherill, L, Agrawal, A, Almasy, L, Brooks, AI, Bucholz, K, Dick, D, Hesselbrock, V, Johnson, EO, Kang, S, Kapoor, M, Kramer, J, Kuperman, S, Madden, PAF, Manz, N, Martin, NG, McClintick, J, Montgomery, GW, Nurnberger, J, Rangaswamy, M, Rice, J, Schuckit, M, Tischfield, JA, Whitfield, JB, Xuei, X, Porjesz, B, Heath, AC, Edenberg, H, Bierut, LJ & Goate, AM 2013, 'A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53', Molecular Psychiatry, vol. 18, no. 11, pp. 1218-1224. https://doi.org/10.1038/mp.2012.143
Wang, J. C. ; Foroud, Tatiana ; Hinrichs, A. L. ; Le, N. X H ; Bertelsen, S. ; Budde, J. P. ; Harari, O. ; Koller, D. L. ; Wetherill, L. ; Agrawal, A. ; Almasy, L. ; Brooks, A. I. ; Bucholz, K. ; Dick, D. ; Hesselbrock, V. ; Johnson, E. O. ; Kang, S. ; Kapoor, M. ; Kramer, J. ; Kuperman, S. ; Madden, P. A F ; Manz, N. ; Martin, N. G. ; McClintick, Jeanette ; Montgomery, G. W. ; Nurnberger, John ; Rangaswamy, M. ; Rice, J. ; Schuckit, M. ; Tischfield, J. A. ; Whitfield, J. B. ; Xuei, Xiaoling ; Porjesz, B. ; Heath, A. C. ; Edenberg, Howard ; Bierut, L. J. ; Goate, A. M. / A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. In: Molecular Psychiatry. 2013 ; Vol. 18, No. 11. pp. 1218-1224.
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