Positive Selection on Loci Associated with Drug and Alcohol Dependence

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 chromosome...

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Main Authors:	Sadler, Brooke, Haller, Gabe, Edenberg, Howard, Tischfield, Jay, Brooks, Andy, Kramer, John, Schuckit, Marc, Nurnberger, John, Goate, Alison
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536217/

id	pubmed-4536217
recordtype	oai_dc
spelling	pubmed-45362172015-08-20 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 Research Article 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. Public Library of Science 2015-08-13 /pmc/articles/PMC4536217/ /pubmed/26270548 http://dx.doi.org/10.1371/journal.pone.0134393 Text en © 2015 Sadler et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sadler, Brooke Haller, Gabe Edenberg, Howard Tischfield, Jay Brooks, Andy Kramer, John Schuckit, Marc Nurnberger, John Goate, Alison
spellingShingle	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
author_facet	Sadler, Brooke Haller, Gabe Edenberg, Howard Tischfield, Jay Brooks, Andy Kramer, John Schuckit, Marc Nurnberger, John Goate, Alison
author_sort	Sadler, Brooke
title	Positive Selection on Loci Associated with Drug and Alcohol Dependence
title_short	Positive Selection on Loci Associated with Drug and Alcohol Dependence
title_full	Positive Selection on Loci Associated with Drug and Alcohol Dependence
title_fullStr	Positive Selection on Loci Associated with Drug and Alcohol Dependence
title_full_unstemmed	Positive Selection on Loci Associated with Drug and Alcohol Dependence
title_sort	positive selection on loci associated with drug and alcohol dependence
description	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.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536217/
_version_	1613259563252842496

Positive Selection on Loci Associated with Drug and Alcohol Dependence

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