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

研究成果: ジャーナルへの寄稿学術誌査読

28 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号1977
ジャーナルNature communications
9
1
DOI
出版ステータス出版済み - 12月 1 2018
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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