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 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

doi:10.1093/jnci/djw167

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

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 language	English (US)
Article number	djw167
Journal	Journal of the National Cancer Institute
Volume	108
Issue number	12
DOIs	https://doi.org/10.1093/jnci/djw167
State	Published - Dec 1 2016
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jnci/djw167

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Zuber, V., Marconett, C. N., Shi, J., Hua, X., Wheeler, W., Yang, C., Song, L., Dale, A. M., Laplana, M., Risch, A., Witoelar, A., Thompson, W. K., Schork, A. J., Bettella, F., Wang, Y., Djurovic, S., Zhou, B., Borok, Z., Van Der Heijden, H. F. M., ... Landi, M. T. (2016). Pleiotropic analysis of lung cancer and blood triglycerides. Journal of the National Cancer Institute, 108(12), [djw167]. https://doi.org/10.1093/jnci/djw167

Zuber, V, Marconett, CN, Shi, J, Hua, X, Wheeler, W, Yang, C, Song, L, Dale, AM, Laplana, M, Risch, A, Witoelar, A, Thompson, WK, Schork, AJ, Bettella, F, Wang, Y, Djurovic, S, Zhou, B, Borok, Z, Van Der Heijden, HFM, De Graaf, J, Swinkels, D, Aben, KK, McKay, J, Hung, RJ, Bikeböller, H, Stevens, VL, Albanes, D, Caporaso, NE, Han, Y, Wei, Y, Panadero, MA, Mayordomo, JI, Christiani, DC, Kiemeney, L, Andreassen, OA, Houlston, R, Amos, CI, Chatterjee, N, Laird-Offringa, IA, Mills, IG & Landi, MT 2016, 'Pleiotropic analysis of lung cancer and blood triglycerides', Journal of the National Cancer Institute, vol. 108, no. 12, djw167. https://doi.org/10.1093/jnci/djw167

@article{f13003b361b44b66991cceea47eb5727,

title = "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.",

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

note = "Funding Information: Epigenetics: This study was supported by NIH grant 1 R01 HL114094 to IAL-O and ZB, NIH grants 1 P30 H101258 and R37HL062569-13 to ZB. ZB is supported by the Ralph Edgington Chair in Medicine. Publisher Copyright: {\textcopyright} The Author 2016. Published by Oxford University Press. All rights reserved.",

year = "2016",

month = dec,

day = "1",

doi = "10.1093/jnci/djw167",

language = "English (US)",

volume = "108",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

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T1 - Pleiotropic analysis of lung cancer and blood triglycerides

AU - Zuber, Verena

AU - Marconett, Crystal N.

AU - Shi, Jianxin

AU - Hua, Xing

AU - Wheeler, William

AU - Yang, Chenchen

AU - Song, Lei

AU - Dale, Anders M.

AU - Laplana, Marina

AU - Risch, Angela

AU - Witoelar, Aree

AU - Thompson, Wesley K.

AU - Schork, Andrew J.

AU - Bettella, Francesco

AU - Wang, Yunpeng

AU - Djurovic, Srdjan

AU - Zhou, Beiyun

AU - Borok, Zea

AU - Van Der Heijden, Henricus F.M.

AU - De Graaf, Jacqueline

AU - Swinkels, Dorine

AU - Aben, Katja K.

AU - McKay, James

AU - Hung, Rayjean J.

AU - Bikeböller, Heike

AU - Stevens, Victoria L.

AU - Albanes, Demetrius

AU - Caporaso, Neil E.

AU - Han, Younghun

AU - Wei, Yongyue

AU - Panadero, Maria Angeles

AU - Mayordomo, Jose I.

AU - Christiani, David C.

AU - Kiemeney, Lambertus

AU - Andreassen, Ole A.

AU - Houlston, Richard

AU - Amos, Christopher I.

AU - Chatterjee, Nilanjan

AU - Laird-Offringa, Ite A.

AU - Mills, Ian G.

AU - Landi, Maria Teresa

N1 - Funding Information: Epigenetics: This study was supported by NIH grant 1 R01 HL114094 to IAL-O and ZB, NIH grants 1 P30 H101258 and R37HL062569-13 to ZB. ZB is supported by the Ralph Edgington Chair in Medicine. Publisher Copyright: © The Author 2016. Published by Oxford University Press. All rights reserved.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

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DO - 10.1093/jnci/djw167

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JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

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ER -

Pleiotropic analysis of lung cancer and blood triglycerides

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