Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: A pathway-based analysis from published GWASs

Yongchu Pan; Hongliang Liu; Yanru Wang; Xiaozheng Kang; Zhensheng Liu; Kouros Owzar; Younghun Han; Li Su; Yongyue Wei; Rayjean J. Hung; Yonathan Brhane; John McLaughlin; Paul Brennan; Heike Bickeböller; Albert Rosenberger; Richard S. Houlston; Neil Caporaso; Maria Teresa Landi; Joachim Heinrich; Angela Risch; Xifeng Wu; Yuanqing Ye; David C. Christiani; Christopher I. Amos; Qingyi Wei

doi:10.1038/srep44634

Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: A pathway-based analysis from published GWASs

Yongchu Pan, Hongliang Liu, Yanru Wang, Xiaozheng Kang, Zhensheng Liu, Kouros Owzar, Younghun Han, Li Su, Yongyue Wei, Rayjean J. Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S. Houlston, Neil Caporaso, Maria Teresa Landi, Joachim Heinrich, Angela RischXifeng Wu, Yuanqing Ye, David C. Christiani, Christopher I. Amos, Qingyi Wei

Epidemiology

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

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Abstract

mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.

Original language	English (US)
Article number	44634
Journal	Scientific reports
Volume	7
DOIs	https://doi.org/10.1038/srep44634
State	Published - Mar 17 2017

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Pan, Y., Liu, H., Wang, Y., Kang, X., Liu, Z., Owzar, K., Han, Y., Su, L., Wei, Y., Hung, R. J., Brhane, Y., McLaughlin, J., Brennan, P., Bickeböller, H., Rosenberger, A., Houlston, R. S., Caporaso, N., Landi, M. T., Heinrich, J., ... Wei, Q. (2017). Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: A pathway-based analysis from published GWASs. Scientific reports, 7, Article 44634. https://doi.org/10.1038/srep44634

Pan, Y, Liu, H, Wang, Y, Kang, X, Liu, Z, Owzar, K, Han, Y, Su, L, Wei, Y, Hung, RJ, Brhane, Y, McLaughlin, J, Brennan, P, Bickeböller, H, Rosenberger, A, Houlston, RS, Caporaso, N, Landi, MT, Heinrich, J, Risch, A, Wu, X, Ye, Y, Christiani, DC, Amos, CI & Wei, Q 2017, 'Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: A pathway-based analysis from published GWASs', Scientific reports, vol. 7, 44634. https://doi.org/10.1038/srep44634

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title = "Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: A pathway-based analysis from published GWASs",

abstract = "mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.",

author = "Yongchu Pan and Hongliang Liu and Yanru Wang and Xiaozheng Kang and Zhensheng Liu and Kouros Owzar and Younghun Han and Li Su and Yongyue Wei and Hung, {Rayjean J.} and Yonathan Brhane and John McLaughlin and Paul Brennan and Heike Bickeb{\"o}ller and Albert Rosenberger and Houlston, {Richard S.} and Neil Caporaso and Landi, {Maria Teresa} and Joachim Heinrich and Angela Risch and Xifeng Wu and Yuanqing Ye and Christiani, {David C.} and Amos, {Christopher I.} and Qingyi Wei",

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doi = "10.1038/srep44634",

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T2 - A pathway-based analysis from published GWASs

AU - Pan, Yongchu

AU - Liu, Hongliang

AU - Wang, Yanru

AU - Kang, Xiaozheng

AU - Liu, Zhensheng

AU - Owzar, Kouros

AU - Han, Younghun

AU - Su, Li

AU - Wei, Yongyue

AU - Hung, Rayjean J.

AU - Brhane, Yonathan

AU - McLaughlin, John

AU - Brennan, Paul

AU - Bickeböller, Heike

AU - Rosenberger, Albert

AU - Houlston, Richard S.

AU - Caporaso, Neil

AU - Landi, Maria Teresa

AU - Heinrich, Joachim

AU - Risch, Angela

AU - Wu, Xifeng

AU - Ye, Yuanqing

AU - Christiani, David C.

AU - Amos, Christopher I.

AU - Wei, Qingyi

PY - 2017/3/17

Y1 - 2017/3/17

N2 - mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.

AB - mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.

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Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: A pathway-based analysis from published GWASs

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