• Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
• Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, USA.
• Massachusetts General Hospital, Boston, Massachusetts, USA.
• Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
• Public Health Ontario, Toronto, Ontario, Canada.
• Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
• Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
• Division of Genetics and Epidemiology, the Institute of Cancer Research, London, United Kingdom.
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
• Helmholtz Centre Munich, German Research Centre for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

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.