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.
Highlights
Consequences of nicotine dependence are the leading cause of preventable death in the USA and it has been noted that some populations experience higher levels of addiction than othersPLOS ONE | DOI:10.1371/journal.pone.0134393 August 13, 2015Selection at Nicotine Dependence Associated Loci determining the diagnosis, prognosis, and treatment of addiction.[1] but the reason for this is not understood
As the program utilized does not incorporate ancestral information, all results are based on the folded frequency spectrum, i.e. the distribution of polymorphic sites according to the number of chromosomes that carry a given minor allele rather than the number of chromosomes that carry the derived, non-ancestral allele. [26]Fig 1 shows regional plots of the Tajima’s D values for the LCT, CHRNA5-A3-B4 nicotinic receptor gene region and the CHRNA6-B3 gene region
Many studies have demonstrated that risk for nicotine addiction has a genetic component
Summary
Consequences of nicotine dependence are the leading cause of preventable death in the USA and it has been noted that some populations experience higher levels of addiction than othersPLOS ONE | DOI:10.1371/journal.pone.0134393 August 13, 2015Selection at Nicotine Dependence Associated Loci determining the diagnosis, prognosis, and treatment of addiction.[1] but the reason for this is not understood. It is challenging to make direct and clear inference on the phenotypic that is the target of natural selection This is true when the phenotype being examined has no obvious evolutionary consequences, and has a disease or traitrelated association with no clear reproductive consequence today, but where patterns of genetic variation are consistent with a positive selective sweep in recent human history. In this case, additional mechanisms and/or alternative explanations must be sought for the existence of selection on the gene of interest. The loci identified in these studies mainly include genes encoding neuronal nicotinic cholinergic receptors (CHRNs)
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