Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease

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Orlando , G , Law , P J , Palin , K , Tuupanen , S , Gylfe , A , Hanninen , U A , Cajuso , T , Tanskanen , T , Kondelin , J , Kaasinen , E , Sarin , A-P , Kaprio , J , Eriksson , J G , Rissanen , H , Knekt , P , Pukkala , E , Jousilahti , P , Salomaa , V , Ripatti , S , Palotie , A , Järvinen , H , Renkonen-Sinisalo , L , Lepisto , A , Bohm , J , Mecklin , J-P , Al-Tassan , N A , Palles , C , Martin , L , Barclay , E , Tenesa , A , Farrington , S , Timofeeva , M N , Meyer , B F , Wakil , S M , Campbell , H , Smith , C G , Idziaszczyk , S , Maughan , T S , Kaplan , R , Kerr , R , Kerr , D , Buchanan , D D , Win , A K , Hopper , J , Jenkins , M , Lindor , N M , Newcomb , P A , Gallinger , S , Conti , D , Schumacher , F , Casey , G , Taipale , J , Cheadle , J P , Dunlop , M G , Tomlinson , I P , Aaltonen , L A & Houlston , R S 2016 , ' Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease ' , Human Molecular Genetics , vol. 25 , no. 11 , pp. 2349-2359 .

Title: Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease
Author: Orlando, Giulia; Law, Philip J.; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G.; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepisto, Anna; Bohm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N.; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Timothy S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Win, Aung Ko; Hopper, John; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P.; Aaltonen, Lauri A.; Houlston, Richard S.
Contributor organization: Research Programs Unit
Lauri Antti Aaltonen / Principal Investigator
Genome-Scale Biology (GSB) Research Program
Department of Medical and Clinical Genetics
Institute for Molecular Medicine Finland
Johan Eriksson / Principal Investigator
Department of General Practice and Primary Health Care
Samuli Olli Ripatti / Principal Investigator
Aarno Palotie / Principal Investigator
Heikki Järvinen / Principal Investigator
Department of Surgery
II kirurgian klinikka
Jussi Taipale / Principal Investigator
Biostatistics Helsinki
Complex Disease Genetics
Genomics of Neurological and Neuropsychiatric Disorders
Genetic Epidemiology
Date: 2016-06-01
Language: eng
Number of pages: 11
Belongs to series: Human Molecular Genetics
ISSN: 0964-6906
Abstract: To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 x 10(-8), odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r(2) = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) <0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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