Exome-wide association study identifies clec3b missense variant p.s106g as being associated with extreme longevity in east asian populations

Kumpei Tanisawa, Yasumichi Arai, Nobuyoshi Hirose, Hiroshi Shimokata, Yoshiji Yamada, Hisashi Kawai, Motonaga Kojima, Shuichi Obuchi, Hirohiko Hirano, Hideyo Yoshida, Hiroyuki Suzuki, Yoshinori Fujiwara, Kazushige Ihara, Maki Sugaya, Tomio Arai, Seijiro Mori, Motoji Sawabe, Noriko Sato, Masaaki Muramatsu, Mitsuru HiguchiYao Wen Liu, Qing Peng Kong, Masashi Tanaka

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6 Citations (Scopus)

Abstract

Life span is a complex trait regulated by multiple genetic and environmental factors; however, the genetic determinants of extreme longevity have been largely unknown. To identify the functional coding variants associated with extreme longevity, we performed an exome-wide association study (EWAS) on a Japanese population by using an Illumina HumanExome Beadchip and a focused replication study on a Chinese population. The EWAS on two independent Japanese cohorts consisting of 530 nonagenarians/centenarians demonstrated that the G allele of CLEC3B missense variant p.S106G was associated with extreme longevity at the exome-wide level of significance (p = 2.33 × 10-7, odds ratio [OR] = 1.50). The CLEC3B gene encodes tetranectin, a protein implicated in the mineralization process in osteogenesis as well as in the prognosis and metastasis of cancer. The replication study consisting of 448 Chinese nonagenarians/centenarians showed that the G allele of CLEC3B p.S106G was also associated with extreme longevity (p = .027, OR = 1.51), and the p value of this variant reached 1.87 × 10-8 in the meta-analysis of Japanese and Chinese populations. In conclusion, the present study identified the CLEC3B p.S106G as a novel longevityassociated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging.

Original languageEnglish
Pages (from-to)309-318
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume72
Issue number3
DOIs
Publication statusPublished - 2017 Jan 1

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Keywords

  • Centenarian
  • Human aging
  • Human genetics
  • Longevity

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Tanisawa, K., Arai, Y., Hirose, N., Shimokata, H., Yamada, Y., Kawai, H., Kojima, M., Obuchi, S., Hirano, H., Yoshida, H., Suzuki, H., Fujiwara, Y., Ihara, K., Sugaya, M., Arai, T., Mori, S., Sawabe, M., Sato, N., Muramatsu, M., ... Tanaka, M. (2017). Exome-wide association study identifies clec3b missense variant p.s106g as being associated with extreme longevity in east asian populations. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 72(3), 309-318. https://doi.org/10.1093/gerona/glw074