Elucidating the genetic architecture of reproductive ageing in the Japanese population

Momoko Horikoshi, Felix R. Day, Masato Akiyama, Makoto Hirata, Yoichiro Kamatani, Koichi Matsuda, Kazuyoshi Ishigaki, Masahiro Kanai, Hollis Wright, Carlos A. Toro, Sergio R. Ojeda, Alejandro Lomniczi, Michiaki Kubo, Ken K. Ong, John R.B. Perry

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10-8) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches.

Original languageEnglish
Article number1977
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2018

Fingerprint

Menopause
Receptor-Like Protein Tyrosine Phosphatases
Genes
Aging of materials
time measurement
Puberty
genes
Gene expression
Gonadotropin-Releasing Hormone
Population
primates
rodents
phosphatases
gene expression
tyrosine
Population Genetics
loci
Gene Frequency
Primates
Rodentia

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Horikoshi, M., Day, F. R., Akiyama, M., Hirata, M., Kamatani, Y., Matsuda, K., ... Perry, J. R. B. (2018). Elucidating the genetic architecture of reproductive ageing in the Japanese population. Nature Communications, 9(1), [1977]. https://doi.org/10.1038/s41467-018-04398-z
Horikoshi, Momoko ; Day, Felix R. ; Akiyama, Masato ; Hirata, Makoto ; Kamatani, Yoichiro ; Matsuda, Koichi ; Ishigaki, Kazuyoshi ; Kanai, Masahiro ; Wright, Hollis ; Toro, Carlos A. ; Ojeda, Sergio R. ; Lomniczi, Alejandro ; Kubo, Michiaki ; Ong, Ken K. ; Perry, John R.B. / Elucidating the genetic architecture of reproductive ageing in the Japanese population. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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Horikoshi, M, Day, FR, Akiyama, M, Hirata, M, Kamatani, Y, Matsuda, K, Ishigaki, K, Kanai, M, Wright, H, Toro, CA, Ojeda, SR, Lomniczi, A, Kubo, M, Ong, KK & Perry, JRB 2018, 'Elucidating the genetic architecture of reproductive ageing in the Japanese population', Nature Communications, vol. 9, no. 1, 1977. https://doi.org/10.1038/s41467-018-04398-z

Elucidating the genetic architecture of reproductive ageing in the Japanese population. / Horikoshi, Momoko; Day, Felix R.; Akiyama, Masato; Hirata, Makoto; Kamatani, Yoichiro; Matsuda, Koichi; Ishigaki, Kazuyoshi; Kanai, Masahiro; Wright, Hollis; Toro, Carlos A.; Ojeda, Sergio R.; Lomniczi, Alejandro; Kubo, Michiaki; Ong, Ken K.; Perry, John R.B.

In: Nature Communications, Vol. 9, No. 1, 1977, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Matsuda, Koichi

AU - Ishigaki, Kazuyoshi

AU - Kanai, Masahiro

AU - Wright, Hollis

AU - Toro, Carlos A.

AU - Ojeda, Sergio R.

AU - Lomniczi, Alejandro

AU - Kubo, Michiaki

AU - Ong, Ken K.

AU - Perry, John R.B.

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