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Sökning: onr:"swepub:oai:DiVA.org:uu-427550" > Identifying Novel S...

Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects

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
Lin, Weiqiang (författare)
The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
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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Huyghe, Jeroen (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Bien, Stephanie (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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
Harrison, Tabitha (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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
Qu, Conghui (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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
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
Yuan, Yuan (författare)
The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
Wang, Fangqin (författare)
The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
Bai, Mengqiu (författare)
The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
Abecasis, Goncalo R (författare)
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States
Albanes, Demetrius (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Berndt, Sonja I (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
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
Bishop, D Timothy (författare)
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom
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
Buch, Stephan (författare)
Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany
Burnett-Hartman, Andrea (författare)
Institute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States
Campbell, Peter T (författare)
Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia
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
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
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
Chanock, Stephen J (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Cho, Sang Hee (författare)
Department of Hematology-Oncology, Chonnam National University Hospital, Hwasun, South Korea
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
Chapelle, Albert de la (författare)
Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, OH, Columbus, United States
Feskens, Edith J M (författare)
Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
Gallinger, Steven J (författare)
Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON, Toronto, Canada
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
Goodman, Phyllis J (författare)
SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Gsur, Andrea (författare)
Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria
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
Gunter, Marc J (författare)
Hampe, Jochen (författare)
Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany
Hampel, Heather (författare)
Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States
Hayes, Richard B (författare)
Division of Epidemiology, Department of Population Health, New York University School of Medicine, NY, New York, United States
Hoffmeister, Michael (författare)
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
Kampman, Ellen (författare)
Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
Kang, Hyun Min (författare)
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States
Keku, Temitope O (författare)
Center for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States
Kim, Hyeong Rok (författare)
Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Korea, Hwasun, South Korea
Le Marchand, Loic (författare)
University of Hawaii Cancer Center, HI, Honolulu, United States
Lee, Soo Chin (författare)
National University Cancer Institute, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore
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
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
Lindblom, Annika (författare)
Karolinska Institutet,Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Lindor, Noralane (författare)
Health Sciences Research, Mayo Clinic, AZ, Scottsdale, United States
Milne, Roger L (författare)
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
Murphy, Neil (författare)
Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia
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
Nickerson, Deborah A (författare)
Department of Genome Sciences, University of Washington, WA, Seattle, United States
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
Pearlman, Rachel (författare)
Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States
Pharoah, Paul D P (författare)
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Platz, Elizabeth A (författare)
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States
Potter, John D (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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
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
Schafmayer, Clemens (författare)
Department of General Surgery, University Hospital Rostock, Rostock, Germany
Schmit, Stephanie L (författare)
Schoen, Robert E (författare)
Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States
Schumacher, Fredrick R (författare)
Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States
Slattery, Martha L (författare)
Su, Yu-Ru (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Tangen, Catherine M (författare)
SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Ulrich, Cornelia M (författare)
Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States
van Duijnhoven, Franzel J B (författare)
van Guelpen, Bethany (författare)
Umeå universitet,Onkologi
Visvanathan, Kala (författare)
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States
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
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
Vymetalkova, Veronika (författare)
Wang, Xiaolong (författare)
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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
Wolk, Alicja (författare)
Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Woods, Michael O (författare)
Memorial University of Newfoundland, Discipline of Genetics, St John's, NL, Canada
Casey, Graham (författare)
Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States
Hsu, Li (författare)
Jenkins, Mark A (författare)
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia
Gruber, Stephen B (författare)
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
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.
Ingår i: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 160:4, s. 1164-1178
  • Tidskriftsartikel (refereegranskat)
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
Lin, Weiqiang
Wen, Wanqing
Huyghe, Jeroen
Bien, Stephanie
Cai, Qiuyin
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Harrison, Tabith ...
Chen, Zhishan
Qu, Conghui
Bao, Jiandong
Long, Jirong
Yuan, Yuan
Wang, Fangqin
Bai, Mengqiu
Abecasis, Goncal ...
Albanes, Demetri ...
Berndt, Sonja I
Bézieau, Stéphan ...
Bishop, D Timoth ...
Brenner, Hermann
Buch, Stephan
Burnett-Hartman, ...
Campbell, Peter ...
Castellví-Bel, S ...
Chan, Andrew T
Chang-Claude, Je ...
Chanock, Stephen ...
Cho, Sang Hee
Conti, David V
Chapelle, Albert ...
Feskens, Edith J ...
Gallinger, Steve ...
Giles, Graham G
Goodman, Phyllis ...
Gsur, Andrea
Guinter, Mark
Gunter, Marc J
Hampe, Jochen
Hampel, Heather
Hayes, Richard B
Hoffmeister, Mic ...
Kampman, Ellen
Kang, Hyun Min
Keku, Temitope O
Kim, Hyeong Rok
Le Marchand, Loi ...
Lee, Soo Chin
Li, Christopher ...
Li, Li
Lindblom, Annika
Lindor, Noralane
Milne, Roger L
Moreno, Victor
Murphy, Neil
Newcomb, Polly A
Nickerson, Debor ...
Offit, Kenneth
Pearlman, Rachel
Pharoah, Paul D ...
Platz, Elizabeth ...
Potter, John D
Rennert, Gad
Sakoda, Lori C
Schafmayer, Clem ...
Schmit, Stephani ...
Schoen, Robert E
Schumacher, Fred ...
Slattery, Martha ...
Su, Yu-Ru
Tangen, Catherin ...
Ulrich, Cornelia ...
van Duijnhoven, ...
van Guelpen, Bet ...
Visvanathan, Kal ...
Vodicka, Pavel
Vodickova, Ludmi ...
Vymetalkova, Ver ...
Wang, Xiaolong
White, Emily
Wolk, Alicja
Woods, Michael O
Casey, Graham
Hsu, Li
Jenkins, Mark A
Gruber, Stephen ...
Peters, Ulrike
Zheng, Wei
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