Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new le...

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Vydané v:	Nature genetics Ročník 54; číslo 8; s. 1167 - 1177
Hlavní autori:	Byun, Jinyoung, Han, Younghun, Li, Yafang, Xia, Jun, Long, Erping, Choi, Jiyeon, Xiao, Xiangjun, Zhu, Meng, Zhou, Wen, Sun, Ryan, Bossé, Yohan, Song, Zhuoyi, Schwartz, Ann, Lusk, Christine, Rafnar, Thorunn, Stefansson, Kari, Zhang, Tongwu, Zhao, Wei, Pettit, Rowland W., Liu, Yanhong, Li, Xihao, Zhou, Hufeng, Walsh, Kyle M., Gorlov, Ivan, Gorlova, Olga, Zhu, Dakai, Rosenberg, Susan M., Pinney, Susan, Bailey-Wilson, Joan E., Mandal, Diptasri, de Andrade, Mariza, Gaba, Colette, Willey, James C., You, Ming, Anderson, Marshall, Wiencke, John K., Albanes, Demetrius, Lam, Stephan, Tardon, Adonina, Chen, Chu, Goodman, Gary, Bojeson, Stig, Brenner, Hermann, Landi, Maria Teresa, Chanock, Stephen J., Johansson, Mattias, Muley, Thomas, Risch, Angela, Wichmann, H.-Erich, Bickeböller, Heike, Christiani, David C., Rennert, Gad, Arnold, Susanne, Field, John K., Shete, Sanjay, Le Marchand, Loic, Melander, Olle, Brunnstrom, Hans, Liu, Geoffrey, Andrew, Angeline S., Kiemeney, Lambertus A., Shen, Hongbing, Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Patel, Alpa, Lan, Qing, Rothman, Nathaniel, Taylor, Fiona, Kachuri, Linda, Witte, John S., Sakoda, Lori C., Spitz, Margaret, Brennan, Paul, Lin, Xihong, McKay, James, Hung, Rayjean J., Amos, Christopher I.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.08.2022 Nature Publishing Group
Predmet:	38/39 38/62 45/43 631/208/205/2138 631/67/1612 Agriculture Animal Genetics and Genomics Basic Medicine Biomedical and Life Sciences Biomedicine Cancer Research Damage Datasets Deoxyribonucleic acid DNA DNA damage DNA-Binding Proteins - genetics Fibroblasts Gene Function Gene mapping Genes Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Human Genetics Humans Interferon regulatory factor 4 Lung cancer Lung Neoplasms - genetics Medical and Health Sciences Medical Genetics and Genomics (including Gene Therapy) Medicin och hälsovetenskap Medicinsk genetik och genomik (Här ingår: Genterapi) Medicinska och farmaceutiska grundvetenskaper Meta-analysis Pleiotropy Polymorphism, Single Nucleotide - genetics Population Populations Quality control Quantitative trait loci Quantitative Trait Loci - genetics RNA-Binding Proteins - genetics Validation studies
ISSN:	1061-4036, 1546-1718, 1546-1718
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Popis
Shrnutí:	To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6 , showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1 . DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4 , potentially exert effects by promoting endogenous DNA damage. A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.
Bibliografia:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 These authors have equal contributions. Author Contributions: J.B., Y.H., Y.L., and C.I.A. conceived and designed the study. Y.H. and X.X. acquired the data. Y.H., E.L., J.C., and X.X. performed the analysis. J.X. performed experimental validation. M.Z., W.Z., R.S., A.S., C.L., T.R., L.K., L.S. provided substantial support on validation study. J.B., Y.H., Y.L., J.X., E.L., J.C., and C.I.A. interpreted the results. J.B., J.X., E.L., and J.C. wrote the first draft of the manuscript. J.B., Y.H., J.X., E.L., J.C., and X.X. provided supplementary materials. J.B. and C.I.A. provided supervision and contributed to analyses. All authors reviewed and commented on the manuscript and approved the final version of the manuscript.
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-022-01115-x