GWAS of smoking behaviour in 165,436 Japanese people reveals seven new loci and shared genetic architecture

Nana Matoba, Masato Akiyama, Kazuyoshi Ishigaki, Masahiro Kanai, Atsushi Takahashi, Yukihide Momozawa, Shiro Ikegawa, Masashi Ikeda, Nakao Iwata, Makoto Hirata, Koichi Matsuda, Michiaki Kubo, Yukinori Okada and Yoichiro Kamatani ()
Additional contact information
Nana Matoba: RIKEN Center for Integrative Medical Sciences
Masato Akiyama: RIKEN Center for Integrative Medical Sciences
Kazuyoshi Ishigaki: RIKEN Center for Integrative Medical Sciences
Masahiro Kanai: RIKEN Center for Integrative Medical Sciences
Atsushi Takahashi: RIKEN Center for Integrative Medical Sciences
Yukihide Momozawa: RIKEN Center for Integrative Medical Sciences
Shiro Ikegawa: RIKEN Center for Integrative Medical Sciences
Masashi Ikeda: Fujita Health University School of Medicine
Nakao Iwata: Fujita Health University School of Medicine
Makoto Hirata: The University of Tokyo
Koichi Matsuda: The University of Tokyo
Michiaki Kubo: RIKEN Center for Integrative Medical Sciences
Yukinori Okada: RIKEN Center for Integrative Medical Sciences
Yoichiro Kamatani: RIKEN Center for Integrative Medical Sciences

Nature Human Behaviour, 2019, vol. 3, issue 5, 471-477

Abstract: Abstract Cigarette smoking is a risk factor for a wide range of human diseases1. To investigate the genetic components associated with smoking behaviours in the Japanese population, we conducted a genome-wide association study of four smoking-related traits using up to 165,436 individuals. In total, we identified seven new loci, including three loci associated with the number of cigarettes per day (EPHX2–CLU, RET and CUX2–ALDH2), three loci associated with smoking initiation (DLC1, CXCL12–TMEM72-AS1 and GALR1–SALL3) and LINC01793–MIR4432HG, associated with the age of smoking initiation. Of these, three loci (LINC01793–MIR4432HG, CXCL12–TMEM72-AS1 and GALR1–SALL3) were found by conducting an additional sex-stratified genome-wide association study. This additional analysis showed heterogeneity of effects between sexes. The cross-sex linkage disequilibrium score regression2,3 analysis also indicated that the genetic component of smoking initiation was significantly different between the sexes. Cross-trait linkage disequilibrium score regression analysis and trait-relevant tissue analysis showed that the number of cigarettes per day has a specific genetic background distinct from those of the other three smoking behaviours. We also report 11 diseases that share genetic basis with smoking behaviours. Although the current study should be carefully considered owing to the lack of replication samples, our findings characterized the genetic architecture of smoking behaviours. Further studies in East Asian populations are warranted to confirm our findings.

Date: 2019
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DOI: 10.1038/s41562-019-0557-y

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