Positive selection on loci associated with drug and alcohol dependence

Brooke Sadler, Gabe Haller, Howard Edenberg, Jay Tischfield, Andy Brooks, John Kramer, Marc Schuckit, John Nurnberger, Alison Goate

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.

Original languageEnglish (US)
Article numbere0134393
JournalPLoS One
Volume10
Issue number8
DOIs
StatePublished - Aug 13 2015

Fingerprint

drug abuse
alcohol abuse
Intelligence
Alcoholism
Substance-Related Disorders
Nicotinic Receptors
Nicotine
Genes
nicotine
Alcohols
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 8
Chromosomes
Tobacco Use Disorder
loci
Genetic Selection
Learning
Data storage equipment
Multigene Family
Phenotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sadler, B., Haller, G., Edenberg, H., Tischfield, J., Brooks, A., Kramer, J., ... Goate, A. (2015). Positive selection on loci associated with drug and alcohol dependence. PLoS One, 10(8), [e0134393]. https://doi.org/10.1371/journal.pone.0134393

Positive selection on loci associated with drug and alcohol dependence. / Sadler, Brooke; Haller, Gabe; Edenberg, Howard; Tischfield, Jay; Brooks, Andy; Kramer, John; Schuckit, Marc; Nurnberger, John; Goate, Alison.

In: PLoS One, Vol. 10, No. 8, e0134393, 13.08.2015.

Research output: Contribution to journalArticle

Sadler, B, Haller, G, Edenberg, H, Tischfield, J, Brooks, A, Kramer, J, Schuckit, M, Nurnberger, J & Goate, A 2015, 'Positive selection on loci associated with drug and alcohol dependence', PLoS One, vol. 10, no. 8, e0134393. https://doi.org/10.1371/journal.pone.0134393
Sadler B, Haller G, Edenberg H, Tischfield J, Brooks A, Kramer J et al. Positive selection on loci associated with drug and alcohol dependence. PLoS One. 2015 Aug 13;10(8). e0134393. https://doi.org/10.1371/journal.pone.0134393
Sadler, Brooke ; Haller, Gabe ; Edenberg, Howard ; Tischfield, Jay ; Brooks, Andy ; Kramer, John ; Schuckit, Marc ; Nurnberger, John ; Goate, Alison. / Positive selection on loci associated with drug and alcohol dependence. In: PLoS One. 2015 ; Vol. 10, No. 8.
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