Positive and balancing selection on SLC18A1 gene associated with psychiatric disorders and human‐unique personality traits

Maintenance of genetic variants susceptible to psychiatric disorders is one of the intriguing evolutionary enigmas. The present study detects three psychiatric disorder‐relevant genes (CLSTN2, FAT1, and SLC18A1) that have been under positive selection during the human evolution. In particular, SLC18A1 (vesicular monoamine transporter 1; VMAT1) gene has a human‐unique variant (rs1390938, Thr136Ile), which is associated with bipolar disorders and/or the anxiety‐related personality traits. 136Ile shows relatively high (20–61%) frequency in non‐African populations, and Tajima's D reports a significant peak around the Thr136Ile site, suggesting that this polymorphism has been positively maintained by balancing selection in non‐African populations. Moreover, Coalescent simulations predict that 136Ile originated around 100,000 years ago, the time being generally associated with the Out‐of‐Africa migration of modern humans. Our study sheds new light on a gene in monoamine pathway as a strong candidate contributing to human‐unique psychological traits.