GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation

Chikashi Terao, Yukihide Momozawa, Kazuyoshi Ishigaki, Eiryo Kawakami, Masato Akiyama, Po Ru Loh, Giulio Genovese, Hiroki Sugishita, Tazro Ohta, Makoto Hirata, John R.B. Perry, Koichi Matsuda, Yoshinori Murakami, Michiaki Kubo, Yoichiro Kamatani

研究成果: ジャーナルへの寄稿学術論文査読

56 被引用数 (Scopus)

抄録

Mosaic loss of chromosome Y (mLOY) is frequently observed in the leukocytes of ageing men. However, the genetic architecture and biological mechanisms underlying mLOY are not fully understood. In a cohort of 95,380 Japanese men, we identify 50 independent genetic markers in 46 loci associated with mLOY at a genome-wide significant level, 35 of which are unreported. Lead markers overlap enhancer marks in hematopoietic stem cells (HSCs, P ≤ 1.0 × 10−6). mLOY genome-wide association study signals exhibit polygenic architecture and demonstrate strong heritability enrichment in regions surrounding genes specifically expressed in multipotent progenitor (MPP) cells and HSCs (P ≤ 3.5 × 10−6). ChIP-seq data demonstrate that binding sites of FLI1, a fate-determining factor promoting HSC differentiation into platelets rather than red blood cells (RBCs), show a strong heritability enrichment (P = 1.5 × 10−6). Consistent with these findings, platelet and RBC counts are positively and negatively associated with mLOY, respectively. Collectively, our observations improve our understanding of the mechanisms underlying mLOY.

本文言語英語
論文番号4719
ジャーナルNature communications
10
1
DOI
出版ステータス出版済み - 01-12-2019

All Science Journal Classification (ASJC) codes

  • 化学一般
  • 生化学、遺伝学、分子生物学一般
  • 物理学および天文学一般

フィンガープリント

「GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル