Selection in the dopamine receptor 2 gene: New candidate SNPs for disease-related studies

Dopamine is a major neurotransmitter in the human brain and is associated with various diseases. Schizophrenia, for example, is treated by blocking the dopamine receptors type 2. In 2009, Shaner, Miller and Mintz stated that schizophrenia was the low fitness variant of a highly variable mental trait. We therefore explore whether the dopamine receptor 2 gene (DRD2) underwent any selection processes. We acquired genotype data of the 1000 Genomes project (phase I), which contains 1093 individuals from 14 populations. We included only single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) of over 0.05 in the analysis. This is equivalent to 151 SNPs for DRD2. We used two different approaches (an outlier approach and a Bayesian approach) to detect loci under selection. The combined results of both approaches yielded nine candidate SNPs under balancing selection. While directional selection strongly favours one allele over all others, balancing selection favours more than one allele. All candidates are in the intronic region of the gene and only one (rs12574471) has been mentioned in the literature. Two of our candidate SNPs are located in specific regions of the gene: rs80215768 lies within a promoter flanking region and rs74751335 lies within a transcription factor binding site. We strongly encourage research on our candidate SNPs and their possible phenotypic effects.