Pleiotropy of genetic variants on obesity and smoking phenotypes

Results from the Oncoarray Project of The International Lung Cancer Consortium

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, Jonas Manjer, Kjell Grankvist & 18 others 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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e0185660
JournalPLoS One
Volume12
Issue number9
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Genetic Pleiotropy
pleiotropy
Tobacco
Brain-Derived Neurotrophic Factor
lung neoplasms
Tobacco Products
body mass index
Lung Neoplasms
Body Mass Index
obesity
Obesity
Smoking
Alcohols
Phenotype
phenotype
Single Nucleotide Polymorphism
Testing
loci
Genetic Loci
smoking (habit)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pleiotropy of genetic variants on obesity and smoking phenotypes : Results from the Oncoarray Project of The International Lung Cancer Consortium. / Wang, Tao; Moon, Jee Young; Wu, Yiqun; Amos, Christopher I.; Hung, Rayjean J.; Tardon, Adonina; Andrew, Angeline; Chen, Chu; Christiani, David C.; Albanes, Demetrios; Heijden, Erik H.F.M.van der; Duell, Eric; Rennert, Gadi; Goodman, Gary; Liu, Geoffrey; Mckay, James D.; Yuan, Jian Min; Field, John K.; Manjer, Jonas; Grankvist, Kjell; Kiemeney, Lambertus A.; Marchand, Loic Le; Teare, M. Dawn; Schabath, Matthew B.; Johansson, Mattias; Aldrich, Melinda C.; Davies, Michael; Johansson, Mikael; Tsao, Ming Sound; Caporaso, Neil; Lazarus, Philip; Lam, Stephen; Bojesen, Stig E.; Arnold, Susanne; Wu, Xifeng; Zong, Xuchen; Hong, Yun Chul; Ho, Gloria Y.F.

In: PLoS One, Vol. 12, No. 9, 01.01.2017, p. e0185660.

Research output: Contribution to journalArticle

Wang, T, Moon, JY, Wu, Y, Amos, CI, Hung, RJ, Tardon, A, Andrew, A, Chen, C, Christiani, DC, Albanes, D, Heijden, EHFMVD, Duell, E, Rennert, G, Goodman, G, Liu, G, Mckay, JD, Yuan, JM, Field, JK, Manjer, J, Grankvist, K, Kiemeney, LA, Marchand, LL, Teare, MD, Schabath, MB, Johansson, M, Aldrich, MC, Davies, M, Johansson, M, Tsao, MS, Caporaso, N, Lazarus, P, Lam, S, Bojesen, SE, Arnold, S, Wu, X, Zong, X, Hong, YC & Ho, GYF 2017, 'Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium', PLoS One, vol. 12, no. 9, pp. e0185660. https://doi.org/10.1371/journal.pone.0185660
Wang, Tao ; Moon, Jee Young ; Wu, Yiqun ; Amos, Christopher I. ; Hung, Rayjean J. ; Tardon, Adonina ; Andrew, Angeline ; Chen, Chu ; Christiani, David C. ; Albanes, Demetrios ; Heijden, Erik H.F.M.van der ; Duell, Eric ; Rennert, Gadi ; Goodman, Gary ; Liu, Geoffrey ; Mckay, James D. ; Yuan, Jian Min ; Field, John K. ; Manjer, Jonas ; Grankvist, Kjell ; Kiemeney, Lambertus A. ; Marchand, Loic Le ; Teare, M. Dawn ; Schabath, Matthew B. ; Johansson, Mattias ; Aldrich, Melinda C. ; Davies, Michael ; Johansson, Mikael ; Tsao, Ming Sound ; Caporaso, Neil ; Lazarus, Philip ; Lam, Stephen ; Bojesen, Stig E. ; Arnold, Susanne ; Wu, Xifeng ; Zong, Xuchen ; Hong, Yun Chul ; Ho, Gloria Y.F. / Pleiotropy of genetic variants on obesity and smoking phenotypes : Results from the Oncoarray Project of The International Lung Cancer Consortium. In: PLoS One. 2017 ; Vol. 12, No. 9. pp. e0185660.
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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.",
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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 - Heijden, Erik H.F.M.van der

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 - Marchand, Loic Le

AU - Teare, M. Dawn

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.

PY - 2017/1/1

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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.

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