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; 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

doi:10.1371/journal.pone.0185660

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 GrankvistLambertus 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

Institut for Klinisk Medicin

6 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	e0185660
Tidsskrift	PloS one
Vol/bind	12
Udgave nummer	9
Antal sider	17
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0185660
Status	Udgivet - 1 sep. 2017

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Wang, T., Moon, J.-Y., Wu, Y., Amos, C. I., Hung, R. J., Tardon, A., Andrew, A., Chen, C., Christiani, D. C., Albanes, D., Heijden, E. H. F. M. V. D., Duell, E., Rennert, G., Goodman, G., Liu, G., Mckay, J. D., Yuan, J.-M., Field, J. K., Manjer, J., ... Ho, G. Y. F. (2017). Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium. PloS one, 12(9), Artikel e0185660. https://doi.org/10.1371/journal.pone.0185660

Wang, T, Moon, J-Y, 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, J-M, Field, JK, Manjer, J, Grankvist, K, Kiemeney, LA, Marchand, LL, Teare, MD, Schabath, MB, Johansson, M, Aldrich, MC, Davies, M, Johansson, M, Tsao, M-S, Caporaso, N, Lazarus, P, Lam, S, Bojesen, SE, Arnold, S, Wu, X, Zong, X, Hong, Y-C & 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, bind 12, nr. 9, e0185660. https://doi.org/10.1371/journal.pone.0185660

@article{1e4dcf1982a14eb68958d41b50d25945,

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

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.",

keywords = "Aged, Body Mass Index, Female, Humans, Male, Middle Aged, Obesity, Phenotype, Polymorphism, Single Nucleotide, Smoking, Journal Article",

author = "Tao Wang and Jee-Young Moon and Yiqun Wu and Amos, {Christopher I} and Hung, {Rayjean J} and Adonina Tardon and Angeline Andrew and Chu Chen and Christiani, {David C} and Demetrios Albanes and Heijden, {Erik H F M van der} and Eric Duell and Gadi Rennert and Gary Goodman and Geoffrey Liu and Mckay, {James D} and Jian-Min Yuan and Field, {John K} and Jonas Manjer and Kjell Grankvist and Kiemeney, {Lambertus A} and Marchand, {Loic Le} and Teare, {M Dawn} and Schabath, {Matthew B} and Mattias Johansson and Aldrich, {Melinda C} and Michael Davies and Mikael Johansson and Ming-Sound Tsao and Neil Caporaso and Philip Lazarus and Stephen Lam and Bojesen, {Stig E} and Susanne Arnold and Xifeng Wu and Xuchen Zong and Yun-Chul Hong and Ho, {Gloria Y F}",

year = "2017",

month = sep,

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doi = "10.1371/journal.pone.0185660",

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volume = "12",

journal = "PloS one",

issn = "1932-6203",

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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 - 2017/9/1

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.

KW - Aged

KW - Body Mass Index

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Obesity

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Smoking

KW - Journal Article

U2 - 10.1371/journal.pone.0185660

DO - 10.1371/journal.pone.0185660

M3 - Journal article

C2 - 28957450

SN - 1932-6203

VL - 12

JO - PloS one

JF - PloS one

IS - 9

M1 - e0185660

ER -

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

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