Pleiotropic Analysis of Lung Cancer and Blood Triglycerides

Verena Zuber, Crystal N Marconett, Jianxin Shi, Xing Hua, William Wheeler, Chenchen Yang, Lei Song, Anders M Dale, Marina Laplana, Angela Risch, Aree Witoelar, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Yunpeng Wang, Srdjan Djurovic, Beiyun Zhou, Zea Borok, Henricus F M van der Heijden, Jacqueline de GraafDorine Swinkels, Katja K Aben, James McKay, Rayjean J Hung, Heike Bikeböller, Victoria L Stevens, Demetrius Albanes, Neil E Caporaso, Younghun Han, Yongyue Wei, Maria Angeles Panadero, Jose I Mayordomo, David C Christiani, Lambertus Kiemeney, Ole A Andreassen, Richard Houlston, Christopher I Amos, Nilanjan Chatterjee, Ite A Laird-Offringa, Ian G Mills, Maria Teresa Landi

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Abstract

Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.

Original languageEnglish
Number of pages4
JournalJournal of the National Cancer Institute
Volume108
Issue number12
Early online date22 Jul 2016
DOIs
Publication statusPublished - 2016

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