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Title: Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia
Authors: Fujito, Naoko T.
Satta, Yoko
Hane, Masaya
Matsui, Atsushi
Yashima, Kenta
Kitajima, Ken
Sato, Chihiro
Takahata, Naoyuki
Hayakawa, Toshiyuki
Author's alias: 松井, 淳
Issue Date: 25-Jul-2018
Publisher: Public Library of Science (PLoS)
Journal title: PLOS ONE
Volume: 13
Issue: 7
Thesis number: e0200278
Abstract: A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20–30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.
Rights: © 2018 Fujito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/2433/236647
DOI(Published Version): 10.1371/journal.pone.0200278
PubMed ID: 30044798
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