Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

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.

• Authors: 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 Graaf, Dorine 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
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 108 Issue 12 (12 2016) ISSN: 1460-2105 [Electronic] United States
• PMID: 27565901 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural)
• Copyright: Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

Chemical References

• Triglycerides

Topics

• Cardiovascular Diseases (epidemiology)
• Case-Control Studies
• Chromosomes, Human, Pair 6
• Genetic Pleiotropy
• Genome-Wide Association Study
• Humans
• Lung Neoplasms (blood, epidemiology, genetics)
• Meta-Analysis as Topic
• Polymorphism, Single Nucleotide
• Risk Factors
• Triglycerides (blood, genetics)