The serotonin transporter 5-HTT is encoded by a single gene SLC6A4. Polymorphisms in SLC6A4 has been associated with awide variety of neurological and psychiatric disorders including increased risk of posttraumatic stress disorder, higher likelihood fordepression, obsessive–compulsive disorder (OCD), increased hostility and criminal behaviour. Genes associated with complex diseasesoften exhibit strong signatures of purifying selection compared to others. Further, discernible population specific variation in the signatureof natural selection have been observed for several complex disease-related genes. In this project we aimed to investigate the populationgenetic variation of the serotonin transporter gene (SLC6A4), focussing on the single nucleotide polymorphisms (SNPs). To this end, weemployed 2504 individuals around the globe available in 1000 Genome project Phase III data and classified them into five ethnic groups:Americans (AMR), Europeans (EUR), Africans (AFR), East Asians (EAS) and South Asians (SAS). Principal component analysis (PCA)performed on all annotated SNPs of SLC6A4 depicted clear clustering between Africans and the rest of the world along PC1, and EastAsians and other non-African populations along PC2. Further, these SNPs were found to be under strong selection pressure especiallyamong East Asian populations with significantly high positive cross-population extended haplotype homozygosity scores compared toAfricans, indicating that SLC6A4 has likely undergone a strong selective sweep among the East Asians in the recent past. Our study canpotentially explain the association between polymorphisms in SLC6A4, and major depression and suicidal tendencies among people of EastAsian ancestry and the absence of such associations among people of European ancestry.
Volume 101, 2022
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