Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium
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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, e0185660, 2017.Research output: Contribution to journal › Journal article › peer-review
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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 - 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
Y1 - 2017
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
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e0185660
ER -
ID: 185943750