To determine whether the nicotinic receptor loci are under selection, we used Tajima’s D, and integrated haplotype score (iHS) to examine the landscape of natural selection at three loci previously demonstrated to harbor genetic variants contributing to the risk of nicotine dependence. These tests have different but complementary strengths. Tajima’s D test functions best on recently completed selective sweeps. There are many variables that contribute to how far in the past a sweep can be detected, such as how extreme the sweep was in the first place. Both the mutation rate and the recombination rate affect it as well and vary widely across the genome making generalizations difficult. By contrast, integrated haplotype score iHS functions best for detecting sweeps in progress with alleles at intermediate frequencies, mainly in the range of or after the separation of European, Asian and African populations, during the agricultural phase of human evolution.
