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 . https://doi.org/10.1093/hmg/ddw087

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: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Heikki Järvinen / Principal Investigator
University of Helsinki, Clinicum
University of Helsinki, II kirurgian klinikka
University of Helsinki, Medicum
University of Helsinki, Research Programs Unit
Date: 2016-06-01
Language: eng
Number of pages: 11
Belongs to series: Human Molecular Genetics
ISSN: 0964-6906
URI: http://hdl.handle.net/10138/172641
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.
Subject: GENOME-WIDE ASSOCIATION
SUSCEPTIBILITY LOCI
INTESTINAL INFLAMMATION
FUNCTIONAL VARIATION
CROHNS-DISEASE
COHORT PROFILE
BIRTH COHORT
METAANALYSIS
IMPUTATION
VARIANTS
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
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