Genome-wide association study reveals BET1L associated with survival time in the 137,693 Japanese individuals

Masato Akiyama; Saori Sakaue; Atsushi Takahashi; Kazuyoshi Ishigaki; Makoto Hirata; Koichi Matsuda; Yukihide Momozawa; Yukinori Okada; Toshiharu Ninomiya; Biobank Japan project; Chikashi Terao; Yoshinori Murakami; Michiaki Kubo; Yoichiro Kamatani

doi:10.1038/s42003-023-04491-0

Genome-wide association study reveals BET1L associated with survival time in the 137,693 Japanese individuals

Commun Biol. 2023 Feb 3;6(1):143. doi: 10.1038/s42003-023-04491-0.

Authors

Masato Akiyama^{1

2

3}, Saori Sakaue^{1

2

4}, Atsushi Takahashi^{1

2

5}, Kazuyoshi Ishigaki^{1

2}, Makoto Hirata⁶, Koichi Matsuda⁷, Yukihide Momozawa⁸, Yukinori Okada^{1

2

4

9}, Toshiharu Ninomiya¹⁰; Biobank Japan project; Chikashi Terao^{1

2}, Yoshinori Murakami¹¹, Michiaki Kubo¹², Yoichiro Kamatani^{13

14

15}

Collaborators

Biobank Japan project:
Masaru Koido, Takayuki Morisaki, Akiko Nagai, Yoji Sagiya

Affiliations

¹ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
² Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
³ Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
⁴ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
⁵ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, 564-8565, Japan.
⁶ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
⁷ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
⁸ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
⁹ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁰ Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan.
¹¹ Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
¹² RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹³ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. [email protected].
¹⁴ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. [email protected].
¹⁵ Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan. [email protected].

Abstract

Human lifespan is reported to be heritable. Although previous genome-wide association studies (GWASs) have identified several loci, a limited number of studies have assessed the genetic associations with the real survival information on the participants. We conducted a GWAS to identify loci associated with survival time in the Japanese individuals participated in the BioBank Japan Project by carrying out sex-stratified GWASs involving 78,029 males and 59,664 females. Of them, 31,324 (22.7%) died during the mean follow-up period of 7.44 years. We found a novel locus associated with survival (BET1L; P = 5.89 × 10^-9). By integrating with eQTL data, we detected a significant overlap with eQTL of BET1L in skeletal muscle. A gene-set enrichment analysis showed that genes related to the BCAR1 protein-protein interaction subnetwork influence survival time (P = 1.54 × 10^-7). These findings offer the candidate genes and biological mechanisms associated with human lifespan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

East Asian People
Female
Genetic Predisposition to Disease*
Genome-Wide Association Study*
Humans
Japan
Male
Qc-SNARE Proteins / genetics

Substances

BET1L protein, human
Qc-SNARE Proteins