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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.

SUBMITTER: Zuber V 

PROVIDER: S-EPMC5241892 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

Zuber Verena V   Marconett Crystal N CN   Shi Jianxin J   Hua Xing X   Wheeler William W   Yang Chenchen C   Song Lei L   Dale Anders M AM   Laplana Marina M   Risch Angela A   Witoelar Aree A   Thompson Wesley K WK   Schork Andrew J AJ   Bettella Francesco F   Wang Yunpeng Y   Djurovic Srdjan S   Zhou Beiyun B   Borok Zea Z   van der Heijden Henricus F M HF   de Graaf Jacqueline J   Swinkels Dorine D   Aben Katja K KK   McKay James J   Hung Rayjean J RJ   Bikeböller Heike H   Stevens Victoria L VL   Albanes Demetrius D   Caporaso Neil E NE   Han Younghun Y   Wei Yongyue Y   Panadero Maria Angeles MA   Mayordomo Jose I JI   Christiani David C DC   Kiemeney Lambertus L   Andreassen Ole A OA   Houlston Richard R   Amos Christopher I CI   Chatterjee Nilanjan N   Laird-Offringa Ite A IA   Mills Ian G IG   Landi Maria Teresa MT  

Journal of the National Cancer Institute 20160826 12


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 sub  ...[more]

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