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Chunk #26 — Discussion

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Positive Selection on Loci Associated with Drug and Alcohol Dependence.
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Many studies have demonstrated that risk for nicotine addiction has a genetic component. We performed two tests of selection on chromosomal regions containing the genes encoding five nicotinic receptor subunits and each of these analyses indicate that selection likely occurred at the CHRNB3-A6 locus. Both the Tajima’s D test and iHS point to an ongoing sweep in humans on chromosome 8. In the case of the CHRNB3-A6 locus, all of the extreme values in the Tajima’s D analysis were positive. High positive Tajima’s D values occur when there is an excess of variants in a region with intermediate allele frequencies. This can occur in either balancing selection or ongoing positive selection. We also found extreme iHS values in the CHRNB3-A6 locus. This region fulfills the criteria for a sweep laid out by Voight and colleagues [30], i.e. clustering of extreme iHS values. Extreme values of iHS are unlikely under simple demographic models, and thus can indicate the action of an ongoing selective sweep. Despite the fact that none of the populations had significantly different p-values from the negative control in