rs114205691

This population-based study examined natural selection on nicotinic receptor gene clusters (CHRNB3-A6 on chromosome 8 and CHRNA5-A3-B4 on chromosome 15) using 1000 Genomes data from three populations. Using Tajima's D and integrated haplotype score (iHS) tests, the authors found strong evidence for positive selection in the CHRNB3-A6 region and moderate evidence in CHRNA5-A3-B4. These regions harbor variants previously associated with nicotine dependence (rs16969968, rs1451240) and cocaine dependence. To understand the target of selection, the authors tested variants in COGA subjects (N=492) for association with cognitive phenotypes (WAIS tests) and found one significant association: rs7017612 with WAIS Digit Symbol score (β=0.43, p=0.003), suggesting memory and learning may be the driving force behind selection.