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 Higuchi & 3 others Yao Wen Liu, Qing Peng Kong, Masashi Tanaka

Research output: Contribution to journalArticle

5 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 - 2016

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Exome
Population
Alleles
Odds Ratio
Osteogenesis
Meta-Analysis
Neoplasm Metastasis
Genes
Neoplasms
Proteins

Keywords

  • Centenarian
  • Human aging
  • Human genetics
  • Longevity

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Exome-wide association study identifies clec3b missense variant p.s106g as being associated with extreme longevity in east asian populations. / Tanisawa, Kumpei; Arai, Yasumichi; Hirose, Nobuyoshi; Shimokata, Hiroshi; Yamada, Yoshiji; Kawai, Hisashi; Kojima, Motonaga; Obuchi, Shuichi; Hirano, Hirohiko; Yoshida, Hideyo; Suzuki, Hiroyuki; Fujiwara, Yoshinori; Ihara, Kazushige; Sugaya, Maki; Arai, Tomio; Mori, Seijiro; Sawabe, Motoji; Sato, Noriko; Muramatsu, Masaaki; Higuchi, Mitsuru; Liu, Yao Wen; Kong, Qing Peng; Tanaka, Masashi.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 72, No. 3, 2016, p. 309-318.

Research output: Contribution to journalArticle

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, Higuchi, M, Liu, YW, Kong, QP & Tanaka, M 2016, '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, vol. 72, no. 3, pp. 309-318. https://doi.org/10.1093/gerona/glw074
Tanisawa, Kumpei ; Arai, Yasumichi ; Hirose, Nobuyoshi ; Shimokata, Hiroshi ; Yamada, Yoshiji ; Kawai, Hisashi ; Kojima, Motonaga ; Obuchi, Shuichi ; Hirano, Hirohiko ; Yoshida, Hideyo ; Suzuki, Hiroyuki ; Fujiwara, Yoshinori ; Ihara, Kazushige ; Sugaya, Maki ; Arai, Tomio ; Mori, Seijiro ; Sawabe, Motoji ; Sato, Noriko ; Muramatsu, Masaaki ; Higuchi, Mitsuru ; Liu, Yao Wen ; Kong, Qing Peng ; Tanaka, Masashi. / Exome-wide association study identifies clec3b missense variant p.s106g as being associated with extreme longevity in east asian populations. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2016 ; Vol. 72, No. 3. pp. 309-318.
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AU - Arai, Yasumichi

AU - Hirose, Nobuyoshi

AU - Shimokata, Hiroshi

AU - Yamada, Yoshiji

AU - Kawai, Hisashi

AU - Kojima, Motonaga

AU - Obuchi, Shuichi

AU - Hirano, Hirohiko

AU - Yoshida, Hideyo

AU - Suzuki, Hiroyuki

AU - Fujiwara, Yoshinori

AU - Ihara, Kazushige

AU - Sugaya, Maki

AU - Arai, Tomio

AU - Mori, Seijiro

AU - Sawabe, Motoji

AU - Sato, Noriko

AU - Muramatsu, Masaaki

AU - Higuchi, Mitsuru

AU - Liu, Yao Wen

AU - Kong, Qing Peng

AU - Tanaka, Masashi

PY - 2016

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N2 - 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.

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