Transcriptome-wide association study reveals candidate causal genes for lung cancer

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Transcriptome-wide association study reveals candidate causal genes for lung cancer. / Bossé, Yohan; Li, Zhonglin; Xia, Jun; Manem, Venkata; Carreras-Torres, Robert; Gabriel, Aurélie; Gaudreault, Nathalie; Albanes, Demetrius; Aldrich, Melinda C.; Andrew, Angeline; Arnold, Susanne; Bickeböller, Heike; Bojesen, Stig E.; Brennan, Paul; Brunnstrom, Hans; Caporaso, Neil; Chen, Chu; Christiani, David C.; Field, John K.; Goodman, Gary; Grankvist, Kjell; Houlston, Richard; Johansson, Mattias; Johansson, Mikael; Kiemeney, Lambertus A.; Lam, Stephen; Landi, Maria T.; Lazarus, Philip; Le Marchand, Loic; Liu, Geoffrey; Melander, Olle; Rennert, Gadi; Risch, Angela; Rosenberg, Susan M.; Schabath, Matthew B.; Shete, Sanjay; Song, Zhuoyi; Stevens, Victoria L.; Tardon, Adonina; Wichmann, H. Erich; Woll, Penella; Zienolddiny, Shan; Obeidat, Ma'en; Timens, Wim; Hung, Rayjean J.; Joubert, Philippe; Amos, Christopher I.; McKay, James D.

In: International Journal of Cancer, Vol. 146, No. 7, 04.2020, p. 1862-1878.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Bossé, Y, Li, Z, Xia, J, Manem, V, Carreras-Torres, R, Gabriel, A, Gaudreault, N, Albanes, D, Aldrich, MC, Andrew, A, Arnold, S, Bickeböller, H, Bojesen, SE, Brennan, P, Brunnstrom, H, Caporaso, N, Chen, C, Christiani, DC, Field, JK, Goodman, G, Grankvist, K, Houlston, R, Johansson, M, Johansson, M, Kiemeney, LA, Lam, S, Landi, MT, Lazarus, P, Le Marchand, L, Liu, G, Melander, O, Rennert, G, Risch, A, Rosenberg, SM, Schabath, MB, Shete, S, Song, Z, Stevens, VL, Tardon, A, Wichmann, HE, Woll, P, Zienolddiny, S, Obeidat, M, Timens, W, Hung, RJ, Joubert, P, Amos, CI & McKay, JD 2020, 'Transcriptome-wide association study reveals candidate causal genes for lung cancer', International Journal of Cancer, vol. 146, no. 7, pp. 1862-1878. https://doi.org/10.1002/ijc.32771

APA

Bossé, Y., Li, Z., Xia, J., Manem, V., Carreras-Torres, R., Gabriel, A., ... McKay, J. D. (2020). Transcriptome-wide association study reveals candidate causal genes for lung cancer. International Journal of Cancer, 146(7), 1862-1878. https://doi.org/10.1002/ijc.32771

Vancouver

Bossé Y, Li Z, Xia J, Manem V, Carreras-Torres R, Gabriel A et al. Transcriptome-wide association study reveals candidate causal genes for lung cancer. International Journal of Cancer. 2020 Apr;146(7):1862-1878. https://doi.org/10.1002/ijc.32771

Author

Bossé, Yohan ; Li, Zhonglin ; Xia, Jun ; Manem, Venkata ; Carreras-Torres, Robert ; Gabriel, Aurélie ; Gaudreault, Nathalie ; Albanes, Demetrius ; Aldrich, Melinda C. ; Andrew, Angeline ; Arnold, Susanne ; Bickeböller, Heike ; Bojesen, Stig E. ; Brennan, Paul ; Brunnstrom, Hans ; Caporaso, Neil ; Chen, Chu ; Christiani, David C. ; Field, John K. ; Goodman, Gary ; Grankvist, Kjell ; Houlston, Richard ; Johansson, Mattias ; Johansson, Mikael ; Kiemeney, Lambertus A. ; Lam, Stephen ; Landi, Maria T. ; Lazarus, Philip ; Le Marchand, Loic ; Liu, Geoffrey ; Melander, Olle ; Rennert, Gadi ; Risch, Angela ; Rosenberg, Susan M. ; Schabath, Matthew B. ; Shete, Sanjay ; Song, Zhuoyi ; Stevens, Victoria L. ; Tardon, Adonina ; Wichmann, H. Erich ; Woll, Penella ; Zienolddiny, Shan ; Obeidat, Ma'en ; Timens, Wim ; Hung, Rayjean J. ; Joubert, Philippe ; Amos, Christopher I. ; McKay, James D. / Transcriptome-wide association study reveals candidate causal genes for lung cancer. In: International Journal of Cancer. 2020 ; Vol. 146, No. 7. pp. 1862-1878.

Bibtex

@article{37b755eb2fea44d2a97ad70b7fd49c66,
title = "Transcriptome-wide association study reveals candidate causal genes for lung cancer",
abstract = "We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.",
keywords = "GWAS, lung cancer, lung eQTL, transcriptome-wide association study",
author = "Yohan Boss{\'e} and Zhonglin Li and Jun Xia and Venkata Manem and Robert Carreras-Torres and Aur{\'e}lie Gabriel and Nathalie Gaudreault and Demetrius Albanes and Aldrich, {Melinda C.} and Angeline Andrew and Susanne Arnold and Heike Bickeb{\"o}ller and Bojesen, {Stig E.} and Paul Brennan and Hans Brunnstrom and Neil Caporaso and Chu Chen and Christiani, {David C.} and Field, {John K.} and Gary Goodman and Kjell Grankvist and Richard Houlston and Mattias Johansson and Mikael Johansson and Kiemeney, {Lambertus A.} and Stephen Lam and Landi, {Maria T.} and Philip Lazarus and {Le Marchand}, Loic and Geoffrey Liu and Olle Melander and Gadi Rennert and Angela Risch and Rosenberg, {Susan M.} and Schabath, {Matthew B.} and Sanjay Shete and Zhuoyi Song and Stevens, {Victoria L.} and Adonina Tardon and Wichmann, {H. Erich} and Penella Woll and Shan Zienolddiny and Ma'en Obeidat and Wim Timens and Hung, {Rayjean J.} and Philippe Joubert and Amos, {Christopher I.} and McKay, {James D.}",
year = "2020",
month = "4",
doi = "10.1002/ijc.32771",
language = "English",
volume = "146",
pages = "1862--1878",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "JohnWiley & Sons, Inc.",
number = "7",

}

RIS

TY - JOUR

T1 - Transcriptome-wide association study reveals candidate causal genes for lung cancer

AU - Bossé, Yohan

AU - Li, Zhonglin

AU - Xia, Jun

AU - Manem, Venkata

AU - Carreras-Torres, Robert

AU - Gabriel, Aurélie

AU - Gaudreault, Nathalie

AU - Albanes, Demetrius

AU - Aldrich, Melinda C.

AU - Andrew, Angeline

AU - Arnold, Susanne

AU - Bickeböller, Heike

AU - Bojesen, Stig E.

AU - Brennan, Paul

AU - Brunnstrom, Hans

AU - Caporaso, Neil

AU - Chen, Chu

AU - Christiani, David C.

AU - Field, John K.

AU - Goodman, Gary

AU - Grankvist, Kjell

AU - Houlston, Richard

AU - Johansson, Mattias

AU - Johansson, Mikael

AU - Kiemeney, Lambertus A.

AU - Lam, Stephen

AU - Landi, Maria T.

AU - Lazarus, Philip

AU - Le Marchand, Loic

AU - Liu, Geoffrey

AU - Melander, Olle

AU - Rennert, Gadi

AU - Risch, Angela

AU - Rosenberg, Susan M.

AU - Schabath, Matthew B.

AU - Shete, Sanjay

AU - Song, Zhuoyi

AU - Stevens, Victoria L.

AU - Tardon, Adonina

AU - Wichmann, H. Erich

AU - Woll, Penella

AU - Zienolddiny, Shan

AU - Obeidat, Ma'en

AU - Timens, Wim

AU - Hung, Rayjean J.

AU - Joubert, Philippe

AU - Amos, Christopher I.

AU - McKay, James D.

PY - 2020/4

Y1 - 2020/4

N2 - We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.

AB - We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.

KW - GWAS

KW - lung cancer

KW - lung eQTL

KW - transcriptome-wide association study

UR - http://www.scopus.com/inward/record.url?scp=85076520927&partnerID=8YFLogxK

U2 - 10.1002/ijc.32771

DO - 10.1002/ijc.32771

M3 - Journal article

C2 - 31696517

AN - SCOPUS:85076520927

VL - 146

SP - 1862

EP - 1878

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 7

ER -

ID: 249431330