Dataset Information

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.

SUBMITTER: Wang T

PROVIDER: S-EPMC5619832 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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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 T Moon Jee-Young JY Wu Yiqun Y Amos Christopher I CI Hung Rayjean J RJ Tardon Adonina A Andrew Angeline A Chen Chu C Christiani David C DC Albanes Demetrios D Heijden Erik H F M van der EHFMV Duell Eric E Rennert Gadi G Goodman Gary G Liu Geoffrey G Mckay James D JD Yuan Jian-Min JM Field John K JK Manjer Jonas J Grankvist Kjell K Kiemeney Lambertus A LA Marchand Loic Le LL Teare M Dawn MD Schabath Matthew B MB Johansson Mattias M Aldrich Melinda C MC Davies Michael M Johansson Mikael M Tsao Ming-Sound MS Caporaso Neil N Lazarus Philip P Lam Stephen S Bojesen Stig E SE Arnold Susanne S Wu Xifeng X Zong Xuchen X Hong Yun-Chul YC Ho Gloria Y F GYF

PloS one 20170928 9

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 signifi ...[more]

PMID: 28957450

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Project description:BackgroundRisk of non-Hodgkin lymphoma (NHL) is higher among individuals with a family history or a prior diagnosis of other cancers. Genome-wide association studies (GWAS) have suggested that some genetic susceptibility variants are associated with multiple complex traits (pleiotropy).ObjectiveWe investigated whether common risk variants identified in cancer GWAS may also increase the risk of developing NHL as the first primary cancer.MethodsAs part of the Population Architecture using Genomics and Epidemiology (PAGE) consortium, 113 cancer risk variants were analyzed in 1,441 NHL cases and 24,183 controls from three studies (BioVU, Multiethnic Cohort Study, Women's Health Initiative) for their association with the risk of overall NHL and common subtypes [diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)] using an additive genetic model adjusted for age, sex and ethnicity. Study-specific results for each variant were meta-analyzed across studies.ResultsThe analysis of NHL subtype-specific GWAS SNPs and overall NHL suggested a shared genetic susceptibility between FL and DLBCL, particularly involving variants in the major histocompatibility complex region (rs6457327 in 6p21.33: FL OR=1.29, p=0.013; DLBCL OR=1.23, p=0.013; NHL OR=1.22, p=5.9 × E-05). In the pleiotropy analysis, six risk variants for other cancers were associated with NHL risk, including variants for lung (rs401681 in TERT: OR per C allele=0.89, p=3.7 × E-03; rs4975616 in TERT: OR per A allele=0.90, p=0.01; rs3131379 in MSH5: OR per T allele=1.16, p=0.03), prostate (rs7679673 in TET2: OR per C allele=0.89, p=5.7 × E-03; rs10993994 in MSMB: OR per T allele=1.09, p=0.04), and breast (rs3817198 in LSP1: OR per C allele=1.12, p=0.01) cancers, but none of these associations remained significant after multiple test correction.ConclusionThis study does not support strong pleiotropic effects of non-NHL cancer risk variants in NHL etiology; however, larger studies are warranted.

Dataset Information

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

Publications

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

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