Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: A genetic association study
| Title: | Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: A genetic association study |
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| Authors: | Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L. Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M.; Annese, Vito; Brand, Stephan; Brant, Steven R.; Cho, Judy H.; Daly, Mark J.; Dubinsky, Marla; Duerr, Richard H.; Ferguson, Lynnette R.; Franke, Andre; Gearry, Richard B.; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R.; Huang, Hailang; Kennedy, Nicholas A.; Kupcinskas, Limas; Lawrance, Ian C.; Lee, James C.; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; Van Der Meulen De Jong, Andrea E; Weersma, Rinse K.; Wilson, David C.; Parkes, Miles; Vermeire, Severine; Rioux, John D.; Mansfield, John; Silverberg, Mark S.; Radford Smith, Graham; Mcgovern, Dermot P. B.; Barrett, Jeffrey C.; Lees, Charlie W; Abraham C; Achkar JP; Ahmad T; Amininejad L; Ananthakrishnan AN; Andersen V; Anderson CA; Andrews JM; Annese V; Aumais G; Baidoo L; Baldassano RN; Bampton PA; Barclay M; Barrett JC; Bayless TM; Bethge J; Bis JC; Bitton A; Boucher G; Brand S; Brandt B; Brant SR; Büning C; Chew A; Cho JH; Cleynen I; Cohain A; Croft A; Daly MJ; D'Amato M; Danese S; De Jong D; De Vos M; Denapiene G; Denson LA; Devaney K; Dewit O; D'Inca R; Dubinsky M; Duerr RH; Edwards C; Ellinghaus D; Essers J; Ferguson LR; Festen EA; Fleshner P; Florin T; Franchimont D; Franke A; Fransen K; Gearry R; Georges M; Gieger C; Glas J; Goyette P; Green T; Griffiths AM; Guthery SL; Hakonarson H; Halfvarson J; Hanigan K; Haritunians T; Hart A; Hawkey C; Hayward NK; Hedl M; Henderson P; Hu X; Huang H; Hui KY; Imielinski M; Ippoliti A; Jonaitis L; Jostins L; Karlsen TH; Kennedy NA; Khan MA; Kiudelis G; Krishnaprasad K; Kugathasan S; Kupcinskas L; Latiano A; Laukens D; Lawrance IC; Lee JC; Lees CW; Leja M; Van Limbergen J; Lionetti P; Liu JZ; Louis E; Mahy G; Mansfield J; Massey D; Mathew CG; McGovern DP; Milgrom R; Mitrovic M; Montgomery GW; Mowat C; Newman W; Ng A; Ng SC; Ng SM; Nikolaus S; Ning K; Nöthen M; Oikonomou I; Palmieri O; Parkes M; Phillips A; Ponsioen CY; Potocnik U; Prescott NJ; Proctor DD; Radford Smith G; Rahier JF; Raychaudhuri S; Regueiro M; Rieder F; Rioux JD; Ripke S; Roberts R; Russell RK; Sanderson JD; Sans M; Satsangi J; Schadt EE; Schreiber S; Schumm LP; Scott R; Seielstad M; Sharma Y; Silverberg MS; Simms LA; Skieceviciene J; Spain SL; Steinhart A; Stempak JM; STRONATI, LAURA; Sventoraityte J; Targan SR; Taylor KM; ter Velde A; Theatre E; Torkvist L; Tremelling M; van der Meulen A; van Sommeren S; Vasiliauskas E; Vermeire S; Verspaget HW; Walters T; Wang K; Wang MH; Weersma RK; Wei Z; Whiteman D; Wijmenga C; Wilson DC; Winkelmann J; Xavier RJ; Zeissig S; Zhang B; Zhang CK; Zhang H; Zhang W; Zhao H; Zhao ZZ |
| Contributors: | Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L. Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M.; Annese, Vito; Brand, Stephan; Brant, Steven R.; Cho, Judy H.; Daly, Mark J.; Dubinsky, Marla; Duerr, Richard H.; Ferguson, Lynnette R.; Franke, Andre; Gearry, Richard B.; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jona; Hov, Johannes R.; Huang, Hailang; Kennedy, Nicholas A.; Kupcinskas, Lima; Lawrance, Ian C.; Lee, James C.; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; Van Der Meulen De Jong, Andrea E; Weersma, Rinse K.; Wilson, David C.; Parkes, Mile; Vermeire, Severine; Rioux, John D.; Mansfield, John; Silverberg, Mark S.; Radford Smith, Graham; Mcgovern, Dermot P. B.; Barrett, Jeffrey C.; Lees, Charlie W; Abraham, C; Achkar, Jp; Ahmad, T; Amininejad, L; Ananthakrishnan, An; Andersen, V; Anderson, Ca; Andrews, Jm; Annese, V; Aumais, G; Baidoo, L; Baldassano, Rn; Bampton, Pa; Barclay, M; Barrett, Jc; Bayless, Tm; Bethge, J; Bis, Jc; Bitton, A; Boucher, G; Brand, S; Brandt, B; Brant, Sr; Büning, C; Chew, A; Cho, Jh; Cleynen, I; Cohain, A; Croft, A; Daly, Mj; D'Amato, M; Danese, S; De Jong, D; De Vos, M; Denapiene, G; Denson, La; Devaney, K; Dewit, O; D'Inca, R; Dubinsky, M; Duerr, Rh; Edwards, C; Ellinghaus, D; Essers, J; Ferguson, Lr; Festen, Ea; Fleshner, P; Florin, T; Franchimont, D; Franke, A; Fransen, K; Gearry, R; Georges, M; Gieger, C; Glas, J; Goyette, P; Green, T; Griffiths, Am |
| Publisher Information: | Lancet Publishing Group |
| Publication Year: | 2016 |
| Collection: | Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: | Medicine (all) |
| Description: | BACKGROUND: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. METHODS: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. FINDINGS: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease ... |
| Document Type: | article in journal/newspaper |
| File Description: | STAMPA |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000368055500032; volume:387; issue:10014; firstpage:156; lastpage:167; numberofpages:12; journal:THE LANCET; http://hdl.handle.net/11573/871160 |
| DOI: | 10.1016/S0140-6736(15)00465-1 |
| Availability: | http://hdl.handle.net/11573/871160; https://doi.org/10.1016/S0140-6736(15)00465-1; http://www.journals.elsevier.com/the-lancet/ |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.2E5DD0A6 |
| Database: | BASE |