Contribution to GWAS and post-GWAS studies of Inflammatory Bowel Disease (IBD)

Our group is an active member of the International IBD Genetics Consortium (IIBDGC). We have conducted our own GWAS and participated in all subsequent meta-analyses leading to the detection of > 200 IBD risk loci.  We have developed sophisticated fine-mapping methods which have contributed to the dissection up to single base pair resolution of 94 risk loci.  We have generated our own dataset (CEDAR-I for Correlated Expression and Disease Association Research) for eQTL analysis in a panel of IBD-relevant cell types in order to identify causative genes in risk loci using an in-house developed colocalisation method.  We have performed large-scale resequencing of candidate genes to prove gene causality using burden tests.

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Key publications

IBD risk loci are enriched in multigenic regulatory modules encompassing causative genes. Momozawa Y, Dmitrieva J, Theatre E, Deffontaine V, Rahmouni S, Charloteaux B, Crins F, Docampo E, Elansary M, Gori A-S, Lecut C, Mariman R, Mni M, Oury C, Altukhov I, Alexeev D, Aulchenko Y, Amininiejad L, Boum G, Hoentjen F, Lowenberg M, Oldenburg B, Pierik MJ, van der Meulen-de Jong AE, van der Woude CJ, Visschedijk MC, The IIBDGC, Lathrop M, Hugot J-P, Weersma RK, De Vos M, Franchimont D, Vermeire S, Kubo M, Louis E, Georges MNat Commun 9:2427 (2018)

Association mapping of inflammatory bowel disease loci to single variant resolution. Huang H*, Fang M*, Jostins L*, Umicevic Mirkov M, Boucher G, Anderson CA, Andersen V, Cleynen I, Cortes A, Crins F, D'Amato M, Deffontaine V, Dmitrieva J, Docampo E, Elansary M, Kai-How Farh K, Franke A, Gori A-S, Goyette P, Halfvarson, Haritunians T, Knight J, Lawrance IC, Lees CW, Louis E, Mariman R, Meuwissen T, Mni M, Momozawa Y, Parkes M, Spain SL, Theatre E, Trynka G, Satsangi J, van Sommeren S, Vermeire S, Xavier RJ, IIBDGC, Weersma R, Duerr RH, Mathew CG, Rioux JD, McGovern DPB, Cho JH, Georges M#, Daly M#, Barrett JC.# *co-first, #co-senior Nature 547: 173-178 (2017)

Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease. Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, Dewit O, Finkel Y,Gassuli MA, Goossens D, Laukens D, Lémann M, Libioulle C, O'Morain C, Reenaers C, Rutgeerts P, Tysk C, Zelenika D, Lathrop M, Del-Favero J, Hugot JP, de Vos M, Franchimont D, Vermeire S, Louis E, Georges MNat Genetics 43:43-47 (2011)

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ; NIDDK IBD Genetics Consortium, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E; Belgian-French IBD Consortium; Wellcome Trust Case Control Consortium, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ. Nat Genetics 40:955-962 (2008)

Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. Libioulle C, Louis E, Hansoul S, Sandor C, Farnir F, Franchimont D, Vermeire S, Dewit O, de Vos M, Dixon A, Demarche B, Gut I, Heath S, Foglio M, Liang L, Laukens D, Mni M, Zelenika D, Van Gossum A, Rutgeerts P, Belaiche J, Lathrop M, Georges MPLoS Genetics 3:e58 (2007)

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