TY - JOUR
T1 - Pleiotropy of genetic variants on obesity and smoking phenotypes
T2 - Results from the oncoarray project of the international lung cancer consortium
AU - Wang, Tao
AU - Moon, Jee Young
AU - Wu, Yiqun
AU - Amos, Christopher I.
AU - Hung, Rayjean J.
AU - Tardon, Adonina
AU - Andrew, Angeline
AU - Chen, Chu
AU - Christiani, David C.
AU - Albanes, Demetrios
AU - van der Heijdendr, Erik H.F.M.
AU - Duell, Eric
AU - Rennert, Gadi
AU - Goodman, Gary
AU - Liu, Geoffrey
AU - McKay, James D.
AU - Yuan, Jian Min
AU - Field, John K.
AU - Manjer, Jonas
AU - Grankvist, Kjell
AU - Kiemeney, Lambertus A.
AU - Le Marchand, Loic
AU - Dawn Teare, M.
AU - Schabath, Matthew B.
AU - Johansson, Mattias
AU - Aldrich, Melinda C.
AU - Davies, Michael
AU - Johansson, Mikael
AU - Tsao, Ming Sound
AU - Caporaso, Neil
AU - Lazarus, Philip
AU - Lam, Stephen
AU - Bojesen, Stig E.
AU - Arnold, Susanne
AU - Wu, Xifeng
AU - Zong, Xuchen
AU - Hong, Yun Chul
AU - Ho, Gloria Y.F.
N1 - Publisher Copyright: © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85032958588
U2 - 10.1371/journal.pone.0185660
DO - 10.1371/journal.pone.0185660
M3 - Article
C2 - 28957450
SN - 1932-6203
VL - 12
JO - PLOS ONE
JF - PLOS ONE
IS - 9
M1 - e0185660
ER -