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 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 (US)
    Article number1977
    JournalNature Communications
    Volume9
    Issue number1
    DOIs
    StatePublished - Dec 1 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

    ASJC Scopus subject areas

    • 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

    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; 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

    Horikoshi, M, Day, FR, Akiyama, M, Hirata, M, Kamatani, Y, Matsuda, K, Ishigaki, K, Kanai, M, Wright, H, Toro, CA, Ojeda, S, 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
    Horikoshi, Momoko ; Day, Felix R. ; Akiyama, Masato ; Hirata, Makoto ; Kamatani, Yoichiro ; Matsuda, Koichi ; Ishigaki, Kazuyoshi ; Kanai, Masahiro ; Wright, Hollis ; Toro, Carlos A. ; Ojeda, Sergio ; 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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