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Identifying Novel S...
Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects
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- Guo, Xingyi (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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- Lin, Weiqiang (författare)
- The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
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- Wen, Wanqing (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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visa fler...
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- Huyghe, Jeroen (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Bien, Stephanie (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Cai, Qiuyin (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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- Harrison, Tabitha (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Chen, Zhishan (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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- Qu, Conghui (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Bao, Jiandong (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States,Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
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- Long, Jirong (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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- Yuan, Yuan (författare)
- The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
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- Wang, Fangqin (författare)
- The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
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- Bai, Mengqiu (författare)
- The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
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- Abecasis, Goncalo R (författare)
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States
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- Albanes, Demetrius (författare)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
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- Berndt, Sonja I (författare)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
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- Bézieau, Stéphane (författare)
- Service de Génétique Médicale, Centre Hospitalier Universitaire, Nantes, France,Department of Preventive Medicine and University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States
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- Bishop, D Timothy (författare)
- Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom
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- Brenner, Hermann (författare)
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany
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- Buch, Stephan (författare)
- Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany
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- Burnett-Hartman, Andrea (författare)
- Institute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States
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- Campbell, Peter T (författare)
- Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia
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- Castellví-Bel, Sergi (författare)
- Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain
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- Chan, Andrew T (författare)
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States
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- Chang-Claude, Jenny (författare)
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany
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- Chanock, Stephen J (författare)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
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- Cho, Sang Hee (författare)
- Department of Hematology-Oncology, Chonnam National University Hospital, Hwasun, South Korea
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- Conti, David V (författare)
- Department of Preventive Medicine and University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States,Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
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- Chapelle, Albert de la (författare)
- Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, OH, Columbus, United States
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- Feskens, Edith J M (författare)
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
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- Gallinger, Steven J (författare)
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON, Toronto, Canada
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- Giles, Graham G (författare)
- Cancer Epidemiology Division, Cancer Council Victoria, Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia
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- Goodman, Phyllis J (författare)
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Gsur, Andrea (författare)
- Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria
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- Guinter, Mark (författare)
- Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia,Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
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Gunter, Marc J (författare)
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- Hampe, Jochen (författare)
- Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany
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- Hampel, Heather (författare)
- Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States
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- Hayes, Richard B (författare)
- Division of Epidemiology, Department of Population Health, New York University School of Medicine, NY, New York, United States
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- Hoffmeister, Michael (författare)
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
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- Kampman, Ellen (författare)
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
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- Kang, Hyun Min (författare)
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States
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- Keku, Temitope O (författare)
- Center for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States
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- Kim, Hyeong Rok (författare)
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Korea, Hwasun, South Korea
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- Le Marchand, Loic (författare)
- University of Hawaii Cancer Center, HI, Honolulu, United States
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- Lee, Soo Chin (författare)
- National University Cancer Institute, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore
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- Li, Christopher I (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States,Department of Family Medicine, University of Virginia, VA, Charlottesville, United States
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- Li, Li (författare)
- Cancer Epidemiology Division, Cancer Council Victoria, Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia,Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States,Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States,Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Lindblom, Annika (författare)
- Karolinska Institutet,Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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- Lindor, Noralane (författare)
- Health Sciences Research, Mayo Clinic, AZ, Scottsdale, United States
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Milne, Roger L (författare)
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- Moreno, Victor (författare)
- Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER Epidemiología y Salud Pública, Madrid, Spain
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- Murphy, Neil (författare)
- Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia
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- Newcomb, Polly A (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States
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- Nickerson, Deborah A (författare)
- Department of Genome Sciences, University of Washington, WA, Seattle, United States
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- Offit, Kenneth (författare)
- Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY, New York, United States; Department of Medicine, Weill Cornell Medical College, NY, New York, United States
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- Pearlman, Rachel (författare)
- Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States
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- Pharoah, Paul D P (författare)
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
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- Platz, Elizabeth A (författare)
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States
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- Potter, John D (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Rennert, Gad (författare)
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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- Sakoda, Lori C (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States
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- Schafmayer, Clemens (författare)
- Department of General Surgery, University Hospital Rostock, Rostock, Germany
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Schmit, Stephanie L (författare)
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- Schoen, Robert E (författare)
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States
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- Schumacher, Fredrick R (författare)
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States
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Slattery, Martha L (författare)
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- Su, Yu-Ru (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Tangen, Catherine M (författare)
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Ulrich, Cornelia M (författare)
- Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States
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van Duijnhoven, Franzel J B (författare)
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- van Guelpen, Bethany (författare)
- Umeå universitet,Onkologi
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- Visvanathan, Kala (författare)
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States
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- Vodicka, Pavel (författare)
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
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- Vodickova, Ludmila (författare)
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
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Vymetalkova, Veronika (författare)
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- Wang, Xiaolong (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- White, Emily (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States
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- Wolk, Alicja (författare)
- Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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- Woods, Michael O (författare)
- Memorial University of Newfoundland, Discipline of Genetics, St John's, NL, Canada
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- Casey, Graham (författare)
- Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States
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Hsu, Li (författare)
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- Jenkins, Mark A (författare)
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia
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Gruber, Stephen B (författare)
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- Peters, Ulrike (författare)
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States
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- Zheng, Wei (författare)
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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(creator_code:org_t)
- Elsevier, 2020
- 2020
- Engelska.
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Ingår i: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 160:4, s. 1164-1178
- Relaterad länk:
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http://www.gastrojou...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Background and Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes.Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted.Results: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis.Conclusions: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Colorectal Cancer
- Susceptibility Genes
- TWAS
- CABLES2
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Guo, Xingyi
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Lin, Weiqiang
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Wen, Wanqing
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Huyghe, Jeroen
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Bien, Stephanie
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Cai, Qiuyin
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visa fler...
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Harrison, Tabith ...
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Chen, Zhishan
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Qu, Conghui
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Bao, Jiandong
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Long, Jirong
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Yuan, Yuan
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Wang, Fangqin
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Bai, Mengqiu
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Abecasis, Goncal ...
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Albanes, Demetri ...
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Berndt, Sonja I
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Bézieau, Stéphan ...
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Bishop, D Timoth ...
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Brenner, Hermann
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Buch, Stephan
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Burnett-Hartman, ...
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Campbell, Peter ...
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Castellví-Bel, S ...
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Chan, Andrew T
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Chang-Claude, Je ...
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Chanock, Stephen ...
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Cho, Sang Hee
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Conti, David V
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Chapelle, Albert ...
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Feskens, Edith J ...
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Gallinger, Steve ...
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Giles, Graham G
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Goodman, Phyllis ...
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Gsur, Andrea
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Guinter, Mark
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Gunter, Marc J
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Hampe, Jochen
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Hampel, Heather
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Hayes, Richard B
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Hoffmeister, Mic ...
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Kampman, Ellen
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Kang, Hyun Min
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Keku, Temitope O
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Kim, Hyeong Rok
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Le Marchand, Loi ...
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Lee, Soo Chin
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Li, Christopher ...
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Li, Li
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Lindblom, Annika
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Lindor, Noralane
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Milne, Roger L
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Moreno, Victor
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Murphy, Neil
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Newcomb, Polly A
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Nickerson, Debor ...
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Offit, Kenneth
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Pearlman, Rachel
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Pharoah, Paul D ...
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Platz, Elizabeth ...
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Potter, John D
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Rennert, Gad
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Sakoda, Lori C
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Schafmayer, Clem ...
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Schmit, Stephani ...
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Schoen, Robert E
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Schumacher, Fred ...
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Slattery, Martha ...
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Su, Yu-Ru
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Tangen, Catherin ...
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Ulrich, Cornelia ...
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van Duijnhoven, ...
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van Guelpen, Bet ...
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Visvanathan, Kal ...
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Vodicka, Pavel
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Vodickova, Ludmi ...
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Vymetalkova, Ver ...
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Wang, Xiaolong
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White, Emily
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Wolk, Alicja
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Woods, Michael O
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Casey, Graham
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Hsu, Li
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Jenkins, Mark A
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Gruber, Stephen ...
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Peters, Ulrike
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Zheng, Wei
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
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Gastroenterology
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Uppsala universitet
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Karolinska Institutet
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Umeå universitet