Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population.

Serotonin-transporter-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the promoter region of serotonin transporter gene, is classified into short (S) and long (L) alleles. Initial case-control association studies claiming the risks of the S allele in depression and anxiety were not completely supported by recent studies. However, most studies, especially those on East Asian populations, have overlooked the complexity of 5-HTTLPR, which involves multiple different alleles with distinct functional properties. To address this issue, distinguishing multiple 5-HTTLPR alleles is essential. Here, using the 5-HTTLPR genotypes previously determined by exhaustive Sanger sequencing of approximately 1,500 Japanese subjects and their comprehensive SNP data, we constructed a method for 5-HTTLPR genotype imputation. We identified 28 tag SNPs for the imputation of four major 5-HTTLPR alleles, which collectively account for 97.6% of 5-HTTLPR alleles in the Japanese population. Our imputation method, achieved an accuracy of 0.872 in cross-validation, will contribute to association analysis of 5-HTTLPR in the Japanese subjects.
Competing Interests: Competing interests: Some of the authors declared financial and non-financial relationships and activities, and conflicts of interest regarding this manuscript as indicated in the supplementary materials. The sponsor had no role in study design, data collection, data analysis, data interpretation or writing of the report.
(© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)