Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium

Research output: Contribution to journalArticle

Abstract

Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p<0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p<0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) achieved statistical significance after Bonferroni correction for multiple testing, and three suggestive SNPs (rs13021737, TMEM18; rs11583200, ELAVL4; and rs6990042, SGCZ) achieved a nominal statistical significance. Our results suggest that there is a common genetic component between BMI and smoking, and pleiotropy analysis can be useful to identify novel genetic loci of complex phenotypes.

Details

Authors
  • Tao Wang
  • Jee Young Moon
  • Yiqun Wu
  • Christopher I. Amos
  • Rayjean J. Hung
  • Adonina Tardon
  • Angeline Andrew
  • Chu Chen
  • David C. Christiani
  • Demetrios Albanes
  • Erik H.F.M.van der Heijden
  • Eric Duell
  • Gadi Rennert
  • Gary Goodman
  • Geoffrey Liu
  • James D. Mckay
  • Jian Min Yuan
  • John K. Field
  • Kjell Grankvist
  • Lambertus A. Kiemeney
  • Loic Le Marchand
  • M. Dawn Teare
  • Matthew B. Schabath
  • Mattias Johansson
  • Melinda C. Aldrich
  • Michael Davies
  • Mikael Johansson
  • Ming Sound Tsao
  • Neil Caporaso
  • Philip Lazarus
  • Stephen Lam
  • Stig E. Bojesen
  • Susanne Arnold
  • Xifeng Wu
  • Xuchen Zong
  • Yun Chul Hong
  • Gloria Y.F. Ho
Organisations
External organisations
  • Yeshiva University
  • Peking University
  • Dartmouth College
  • University of Toronto
  • Norris Cotton Cancer Center
  • Fred Hutchinson Cancer Research Center
  • Harvard University
  • National Cancer Institute, USA
  • Radboud University Nijmegen
  • Catalan Institute of Oncology
  • Carmel Medical Center
  • International Agency for Research on Cancer, World Health Organization
  • University of Liverpool
  • Umeå University
  • University of Hawaii
  • University of Sheffield
  • H. Lee Moffitt Cancer Center & Research Institute
  • Vanderbilt University
  • Princess Margaret Hospital University of Toronto
  • Washington State University
  • British Columbia Cancer Agency
  • University of Copenhagen
  • University of Texas
  • Seoul National University
  • University of Oviedo
  • CIBER Epidemiology and Public Health (CIBERESP)
  • University of Pittsburgh
  • Skåne University Hospital
  • Copenhagen University Hospital
  • University of Kentucky
  • Hofstra University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Medical Genetics
Original languageEnglish
Pages (from-to)e0185660
JournalPLoS ONE
Volume12
Issue number9
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes