Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia

Naoko T. Fujito, Yoko Satta, Masaya Hane, Atsushi Matsui, Kenta Yashima, Ken Kitajima, Chihiro Sato, Naoyuki Takahata, Toshiyuki Hayakawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article numbere0200278
JournalPloS one
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

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Schizophrenia
Genes
promoter regions
Sialyltransferases
Single Nucleotide Polymorphism
genes
Genetic Promoter Regions
behavior disorders
social environment
Social Environment
Brain
human population
brain
genomics
loci
CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase
schizophrenia
Population
methodology

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Fujito, N. T., Satta, Y., Hane, M., Matsui, A., Yashima, K., Kitajima, K., ... Hayakawa, T. (2018). Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia. PloS one, 13(7), [e0200278]. https://doi.org/10.1371/journal.pone.0200278

Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia. / Fujito, Naoko T.; Satta, Yoko; Hane, Masaya; Matsui, Atsushi; Yashima, Kenta; Kitajima, Ken; Sato, Chihiro; Takahata, Naoyuki; Hayakawa, Toshiyuki.

In: PloS one, Vol. 13, No. 7, e0200278, 01.07.2018.

Research output: Contribution to journalArticle

Fujito, NT, Satta, Y, Hane, M, Matsui, A, Yashima, K, Kitajima, K, Sato, C, Takahata, N & Hayakawa, T 2018, 'Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia', PloS one, vol. 13, no. 7, e0200278. https://doi.org/10.1371/journal.pone.0200278
Fujito NT, Satta Y, Hane M, Matsui A, Yashima K, Kitajima K et al. Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia. PloS one. 2018 Jul 1;13(7). e0200278. https://doi.org/10.1371/journal.pone.0200278
Fujito, Naoko T. ; Satta, Yoko ; Hane, Masaya ; Matsui, Atsushi ; Yashima, Kenta ; Kitajima, Ken ; Sato, Chihiro ; Takahata, Naoyuki ; Hayakawa, Toshiyuki. / Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia. In: PloS one. 2018 ; Vol. 13, No. 7.
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