Abstract
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.
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Funding
This work was supported by JSPS KAKENHI grant numbers JP23H02840, JP23H03838, and JP22K07583, and by AMED grant number JP19dm0207074, JP23dk0207053, JP24wm0625302, and JP24wm0625001, and by JST Moonshot R&D Grant Number JPMJMS2021.
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Yanagida, Y., Naka, I., Nakachi, Y. et al. Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population. J Hum Genet 70, 41–45 (2025). https://doi.org/10.1038/s10038-024-01296-9
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DOI: https://doi.org/10.1038/s10038-024-01296-9
