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.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Yongchu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Kang
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, USA.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Brhane
authors.affiliation: Public Health Ontario, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeböller
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.affiliation: Division of Genetics and Epidemiology, the Institute of Cancer Research, London, United Kingdom.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Teresa Landi
authors.affiliation: Helmholtz Centre Munich, German Research Centre for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D012333:RNA, Messenger