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

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Tyck till om SwePub Sök här!

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

1 of 1
Previous record
Next record
To hitlist

Details
MARC

Guo, XingyiDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)

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

Article/chapterEnglish2020

Publisher, publication year, extent ...

Elsevier,2020
printrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-427550
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-427550URI
https://doi.org/10.1053/j.gastro.2020.08.062DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:146188541URI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-180798URI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Gastroenterology 2021;160:1164–1178
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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Colorectal Cancer
Susceptibility Genes
TWAS
CABLES2

Added entries (persons, corporate bodies, meetings, titles ...)

Lin, WeiqiangThe Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China (author)
Wen, WanqingDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Huyghe, JeroenDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Bien, StephanieDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Cai, QiuyinDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Harrison, TabithaDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Chen, ZhishanDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Qu, ConghuiDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Bao, JiandongDivision 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 (author)
Long, JirongDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Yuan, YuanThe Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China (author)
Wang, FangqinThe Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China (author)
Bai, MengqiuThe Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China (author)
Abecasis, Goncalo RDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States (author)
Albanes, DemetriusDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (author)
Berndt, Sonja IDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (author)
Bézieau, StéphaneService 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 (author)
Bishop, D TimothyLeeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom (author)
Brenner, HermannDivision 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 (author)
Buch, StephanDepartment of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany (author)
Burnett-Hartman, AndreaInstitute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States (author)
Campbell, Peter TBehavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia (author)
Castellví-Bel, SergiGastroenterology 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 (author)
Chan, Andrew TDivision 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 (author)
Chang-Claude, JennyDivision of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany (author)
Chanock, Stephen JDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (author)
Cho, Sang HeeDepartment of Hematology-Oncology, Chonnam National University Hospital, Hwasun, South Korea (author)
Conti, David VDepartment 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 (author)
Chapelle, Albert de laDepartment of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, OH, Columbus, United States (author)
Feskens, Edith J MDivision of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands (author)
Gallinger, Steven JLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON, Toronto, Canada (author)
Giles, Graham GCancer 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 (author)
Goodman, Phyllis JSWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Gsur, AndreaInstitute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria (author)
Guinter, MarkBehavioral 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 (author)
Gunter, Marc J (author)
Hampe, JochenDepartment of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany (author)
Hampel, HeatherDivision of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States (author)
Hayes, Richard BDivision of Epidemiology, Department of Population Health, New York University School of Medicine, NY, New York, United States (author)
Hoffmeister, MichaelDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany (author)
Kampman, EllenDivision of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands (author)
Kang, Hyun MinDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States (author)
Keku, Temitope OCenter for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States (author)
Kim, Hyeong RokDepartment of Surgery, Chonnam National University Hwasun Hospital and Medical School, Korea, Hwasun, South Korea (author)
Le Marchand, LoicUniversity of Hawaii Cancer Center, HI, Honolulu, United States (author)
Lee, Soo ChinNational University Cancer Institute, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore (author)
Li, Christopher IDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States,Department of Family Medicine, University of Virginia, VA, Charlottesville, United States (author)
Li, LiCancer 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 (author)
Lindblom, AnnikaKarolinska Institutet,Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (author)
Lindor, NoralaneHealth Sciences Research, Mayo Clinic, AZ, Scottsdale, United States (author)
Milne, Roger L (author)
Moreno, VictorOncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER Epidemiología y Salud Pública, Madrid, Spain (author)
Murphy, NeilBehavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia (author)
Newcomb, Polly ADivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States (author)
Nickerson, Deborah ADepartment of Genome Sciences, University of Washington, WA, Seattle, United States (author)
Offit, KennethClinical 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 (author)
Pearlman, RachelDivision of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States (author)
Pharoah, Paul D PDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (author)
Platz, Elizabeth ADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States (author)
Potter, John DDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Rennert, GadDepartment 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 (author)
Sakoda, Lori CDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States (author)
Schafmayer, ClemensDepartment of General Surgery, University Hospital Rostock, Rostock, Germany (author)
Schmit, Stephanie L (author)
Schoen, Robert EDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States (author)
Schumacher, Fredrick RDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States (author)
Slattery, Martha L (author)
Su, Yu-RuDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Tangen, Catherine MSWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Ulrich, Cornelia MHuntsman Cancer Institute and Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States (author)
van Duijnhoven, Franzel J B (author)
van Guelpen, BethanyUmeå universitet,Onkologi(Swepub:umu)beyvan99 (author)
Visvanathan, KalaDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States (author)
Vodicka, PavelDepartment 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 (author)
Vodickova, LudmilaDepartment 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 (author)
Vymetalkova, Veronika (author)
Wang, XiaolongDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
White, EmilyDivision 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 (author)
Wolk, AlicjaKarolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden(Swepub:uu)alwol516 (author)
Woods, Michael OMemorial University of Newfoundland, Discipline of Genetics, St John's, NL, Canada (author)
Casey, GrahamCenter for Public Health Genomics, University of Virginia, VA, Charlottesville, United States (author)
Hsu, Li (author)
Jenkins, Mark ACentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia (author)
Gruber, Stephen B (author)
Peters, UlrikeDivision 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 (author)
Zheng, WeiDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United StatesThe Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China (creator_code:org_t)

Related titles

In:Gastroenterology: Elsevier160:4, s. 1164-11780016-50851528-0012

Internet link

Find in a library

Gastroenterology (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Guo, Xingyi; Lin, Weiqiang; Wen, Wanqing; Huyghe, Jeroen; Bien, Stephanie; Cai, Qiuyin; show more...; 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; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Articles in the publication: Gastroenterology

By the university: Uppsala University; Karolinska Institutet; Umeå University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se