@article{faa80e0f94024a03a7231301e2f95ed2,
title = "Exome-wide association study identifies clec3b missense variant p.s106g as being associated with extreme longevity in east asian populations",
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.",
keywords = "Centenarian, Human aging, Human genetics, Longevity",
author = "Kumpei Tanisawa and Yasumichi Arai and Nobuyoshi Hirose and Hiroshi Shimokata and Yoshiji Yamada and Hisashi Kawai and Motonaga Kojima and Shuichi Obuchi and Hirohiko Hirano and Hideyo Yoshida and Hiroyuki Suzuki and Yoshinori Fujiwara and Kazushige Ihara and Maki Sugaya and Tomio Arai and Seijiro Mori and Motoji Sawabe and Noriko Sato and Masaaki Muramatsu and Mitsuru Higuchi and Liu, {Yao Wen} and Kong, {Qing Peng} and Masashi Tanaka",
note = "Funding Information: This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; by GMEXT/JSPS KAKENHI Grants (A-25242062, A-22240072, B-21390459, C-26670481, C-21590411, and CER-24650414 to M.T.); by MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2015-2019 from the Ministry of Education, Culture, Sports, Science and Technology (S1511017 to M.H.); by Grants-in-Aid for Research on Intractable Diseases (Mitochondrial Disorders; 23-016, 23-116, and 24-005 to M.T.) from the Ministry of Health, Labor, and Welfare of Japan; by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED (15ek0109088h0001 and 15ek0109088s0401 to M.T.); by the Takeda Science Foundation (to M.T.); by the Smoking Research Foundation (to T.A. and M.S.); and by the Joint Usage/Research Program of the Medical Research Institute, Tokyo Medical and Dental University (to M.M.). Publisher Copyright: {\textcopyright} The Author 2016.",
year = "2017",
doi = "10.1093/gerona/glw074",
language = "English",
volume = "72",
pages = "309--318",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "3",
}