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Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia
DR. Brenner, CI. Amos, Y. Brhane, MN. Timofeeva, N. Caporaso, Y. Wang, DC. Christiani, H. Bickeböller, P. Yang, D. Albanes, VL. Stevens, S. Gapstur, J. McKay, P. Boffetta, D. Zaridze, N. Szeszenia-Dabrowska, J. Lissowska, P. Rudnai, E. Fabianova,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, metaanalýza, Research Support, N.I.H., Extramural, práce podpořená grantem
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
Medline Complete (EBSCOhost)
od 1996-01-01 do Před 1 rokem
PubMed
26363033
DOI
10.1093/carcin/bgv128
Knihovny.cz E-zdroje
- MeSH
- adenokarcinom genetika patologie MeSH
- Bayesova věta MeSH
- celogenomová asociační studie MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- nádory plic genetika patologie MeSH
- spinocelulární karcinom genetika patologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16×10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.
Cancer Epidemiology Program University of Hawaii Cancer Center Honolulu HI 96813 USA
Center for Genomic Medicine Graduate School of Medicine Kyoto University Kyoto 606 8501 Japan
Department of Biomedicine University of Bergen Bergen 5009 Norway
Department of Cancer Research and Molecular Medicine Faculty of Medicine
Department of Community Medicine University of Tromso Tromso N 9037 Norway
Department of Epidemiology Institute of Occupational Medicine 91348 Lodz Poland
Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX 77030 USA
Department of Genetics U T M D Anderson Cancer Center Houston TX 77030 USA
Department of Laboratory Medicine Children's and Women's Health Faculty of Medicine and
Department of Oncology Cambridge Biomedical Research Centre Cambridge CB2 0QQ UK
Department of Preventive Medicine Palacky University Olomouc 77515 Czech Republic
Division of Genetics and Epidemiology The Institute of Cancer Research Sutton Surrey SM2 5NG UK
Division of Health Sciences Cancer Center and College of Medicine Mayo Clinic Rochester NY 55905 USA
Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA 98109 USA
Duncan Cancer Center Baylor College of Medicine Houston TX 77030 USA
Institute of Carcinogenesis Russian N N Blokhin Cancer Research Centre 115478 Moscow Russia
Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH8 9YL UK
Institute of Molecular and Cell Biology University of Tartu Tartu 51010 Estonia
Keck School of Medicine University of South California Los Angeles CA 90089 0911 USA and
Lunenfeld Tanenbaum Research Institute of Mount Sinai Hospital Toronto Ontario M5T 3L9 Canada
McGill University and Genome Québec Innovation Centre Montréal Quebec Canada
National Institute of Environmental Health Budapest 1097 Hungary
National Institute of Public Health Bucharest 050463 Romania
Section of Genetics International Agency for Research on Cancer 69372 Lyon France
Unit of Environmental Epidemiology Helmholtz Zentrum Munchen 85764 Neuherberg Germany
Citace poskytuje Crossref.org
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