Common biological networks underlie genetic risk for alcoholism in African- and European-American populations

M. Z. Kos, J. Yan, D. M. Dick, A. Agrawal, K. K. Bucholz, J. P. Rice, E. O. Johnson, M. Schuckit, S. Kuperman, J. Kramer, A. M. Goate, J. A. Tischfield, T. Foroud, J. Nurnberger, V. Hesselbrock, B. Porjesz, L. J. Bierut, H. J. Edenberg, L. Almasy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome-wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome-wide SNPs collectively account for risk of AD in two US populations, African-Americans (AAs) and European-Americans (EAs). Analyzing GWAS data for two independent case-control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P=1.64×10-3 and 2.08×10-4 for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF<0.05) best fit the observed distribution of polymarker signals. When scoring bins were annotated for gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.

Original languageEnglish (US)
Pages (from-to)532-542
Number of pages11
JournalGenes, Brain and Behavior
Volume12
Issue number5
DOIs
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

African Americans
Alcoholism
Genome-Wide Association Study
Population
Genes
Glycine Plasma Membrane Transport Proteins
Gene Regulatory Networks
Ethnic Groups
Substance-Related Disorders
Single Nucleotide Polymorphism
Chlorides
Economics
Genome
Psychology
Health

Keywords

  • Alcohol dependence
  • GWAS
  • Pathway analysis
  • Polymarker scores
  • Rare variants
  • Synthetic association

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Kos, M. Z., Yan, J., Dick, D. M., Agrawal, A., Bucholz, K. K., Rice, J. P., ... Almasy, L. (2013). Common biological networks underlie genetic risk for alcoholism in African- and European-American populations. Genes, Brain and Behavior, 12(5), 532-542. https://doi.org/10.1111/gbb.12043

Common biological networks underlie genetic risk for alcoholism in African- and European-American populations. / Kos, M. Z.; Yan, J.; Dick, D. M.; Agrawal, A.; Bucholz, K. K.; Rice, J. P.; Johnson, E. O.; Schuckit, M.; Kuperman, S.; Kramer, J.; Goate, A. M.; Tischfield, J. A.; Foroud, T.; Nurnberger, J.; Hesselbrock, V.; Porjesz, B.; Bierut, L. J.; Edenberg, H. J.; Almasy, L.

In: Genes, Brain and Behavior, Vol. 12, No. 5, 07.2013, p. 532-542.

Research output: Contribution to journalArticle

Kos, MZ, Yan, J, Dick, DM, Agrawal, A, Bucholz, KK, Rice, JP, Johnson, EO, Schuckit, M, Kuperman, S, Kramer, J, Goate, AM, Tischfield, JA, Foroud, T, Nurnberger, J, Hesselbrock, V, Porjesz, B, Bierut, LJ, Edenberg, HJ & Almasy, L 2013, 'Common biological networks underlie genetic risk for alcoholism in African- and European-American populations', Genes, Brain and Behavior, vol. 12, no. 5, pp. 532-542. https://doi.org/10.1111/gbb.12043
Kos, M. Z. ; Yan, J. ; Dick, D. M. ; Agrawal, A. ; Bucholz, K. K. ; Rice, J. P. ; Johnson, E. O. ; Schuckit, M. ; Kuperman, S. ; Kramer, J. ; Goate, A. M. ; Tischfield, J. A. ; Foroud, T. ; Nurnberger, J. ; Hesselbrock, V. ; Porjesz, B. ; Bierut, L. J. ; Edenberg, H. J. ; Almasy, L. / Common biological networks underlie genetic risk for alcoholism in African- and European-American populations. In: Genes, Brain and Behavior. 2013 ; Vol. 12, No. 5. pp. 532-542.
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