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Nature Genetics, December 2010, Volume 42, Number 12

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Andre Franke, Dermot P B McGovern, Jeffrey C Barrett, Kai Wang, Graham L Radford-Smith, Tariq Ahmad, Charlie W Lees, Tobias Balschun, James Lee, Rebecca Roberts, Carl A Anderson, Joshua C Bis, Suzanne Bumpstead, David Ellinghaus, Eleonora M Festen, Michel Georges, Todd Green, Talin Haritunians, Luke Jostins, Anna Latiano, Christopher G Mathew, Grant W Montgomery, Natalie J Prescott, Soumya Raychaudhuri, Jerome I Rotter, Philip Schumm, Yashoda Sharma, Lisa A Simms, Kent D Taylor, David Whiteman, Cisca Wijmenga, Robert N Baldassano, Murray Barclay, Theodore M Bayless, Stephan Brand, Carsten BÃ¼ning, Albert Cohen, Jean-Frederick Colombel, Mario Cottone, Laura Stronati, Ted Denson, Martine De Vos, Renata D'Inca, Marla Dubinsky, Cathryn Edwards, Tim Florin, Denis Franchimont, Richard Gearry, JÃ¼rgen Glas, Andre Van Gossum, Stephen L Guthery, Jonas Halfvarson, Hein W Verspaget, Jean-Pierre Hugot, Amir Karban, Debby Laukens, Ian Lawrance, Marc Lemann, Arie Levine, CÃ©cile Libioulle, Edouard Louis, Craig Mowat, William Newman, Julian PanÃ©s, Anne Phillips, Deborah D Proctor, Miguel Regueiro, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Frank Seibold, A Hillary Steinhart, Pieter C F Stokkers, Leif Torkvist, Gerd Kullak-Ublick, David Wilson, Thomas Walters, Stephan R Targan, Steven R Brant, John D Rioux, Mauro D'Amato, Rinse K Weersma, Subra Kugathasan, Anne M Griffiths, John C Mansfield, Severine Vermeire, Richard H Duerr, Mark S Silverberg, Jack Satsangi, Stefan Schreiber, Judy H Cho, Vito Annese, Hakon Hakonarson, Mark J Daly & Miles Parkes

abstract

We undertook a meta-analysis of six Crohn’s disease genomewide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10−8).

A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn’s disease.

LIST OF PARTICIPANTS

Legend: Coordinating PI Participants

	1	2	3	4	5	6	7	8	9	10	11	12	13
	BE-SMART	CEDAR-UC	Combined therapy of biologicals and new oral drugs.	DETECT	DNA banking	GENGISCAN	HELP-AID	I-CARE	Immunization	LOVE	PACIFIC	Pediatric	SPARE
AZ Damiaan	x										x		x
AZ Groeninge	x	x					x				x
AZ Maria Middelares		x									x
AZ Sint-Lucas Brugge	x												x
AZ Sint-Lucas Gent							x
AZ Turnhout campus Sint-Jozef							x
CHC Clinique Saint-Joseph - Liège	x			x			x
CHU de Liège site Sart-Tilman	x	x		x		x	x	x			x		x
CHU UCL Namur site Godinne		x	x			x			x		x		x
Clinique Saint-Jean							x
Clinique Saint-Pierre	x						x						x
Hôpital de Joliment			x	x					x	x
Hôpital Erasme	x	x		x	x	x	x	x			x		x
Mariaziekenhuis Noord-Limburg				x			x
Onze Lieve Vrouwziekenhuis campus Aalst	x	x					x				x
UZ Antwerpen							x
UZ Brussel												x
UZ Gent		x		x		x	x						x
UZ Leuven Gasthuisberg	x	x		x		x	x			x	x		x
Ziekenhuis Oost-Limburg campus Sint-Jan							x

	1	2	3	4	5	6	7	8	9	10	11	12	13
	BE-SMART	CEDAR-UC	Combined therapy of biologicals and new oral drugs.	DETECT	DNA banking	GENGISCAN	HELP-AID	I-CARE	Immunization	LOVE	PACIFIC	Pediatric	SPARE
Karen Van Hoeve
- -			x	x					x	x
Leila Amininejad		x			x		x
Saskia Appelmans
Thomas Billiet
Patrick Bontems
Isabelle Bueres
Katrien Bulté
Guillaume Burnet
Peter Burvenich
Philippe Caenepeel
Olivier Cajot
Christophe Claessens							x
Jean-Charles Coche
Jean-Louis Coenegrachts
Arnaud Colard							x
Filip Couturier
Lara Crapé
Anneline Cremer
Anneline Cremer						x		x
Cléo Croonen
Francois D'Heygere	x
Steven De Coninck
Elisabeth De Greef												x
Marc De Maeyer
Marc De Reuck
Elodie De Ruyck
Nicolas de Suray
Martine De Vos				x		x	x						x
Benedicte De Vroey
Astrid De Zutter
Stefan Delen
Marie-Armelle Denis
Pieter Dewint		x									x
Olivier Dewit	x						x						x
Sophie Dewit				x			x
Joris Dutre
Anke Engelen
Marc Etienne
Marc Ferrante	x	x		x			x						x
René Fiasse
Fernand Fontaine	x			x
Denis Franchimont	x			x		x	x				x		x
Silke François
Jeroen Geldof
Bruno Hauser
Pieter Hindryckx		x
Ilse Hoffman
Tom Holvoet
Alice Hoyois
Evelien Humblet							x
Saskia Ilegems
Aranzazu Jauregui Amezaga
Guy Lambrecht	x										x		x
Pierre Lammens
Claire Liefferinckx											x
Triana Lobaton
Edouard Louis				x		x	x				x		x
Elisabeth Macken							x
Marie-Christine Mairlot
Jean-Marc Maisin
Fazia Mana							x
Walter Margos
Fady Mokaddem
Kim Moubax
Vinciane Muls
Carmen Musala
Michele Ngassa
Maja Noman
Hanne Ooms
An Outtier
Romy Ouziel
Harald Peeters
Annelies Posen
Philippe Potvin
Lieven Pouillon
Jean-Francois Rahier		x	x			x			x		x		x
Catherine Reenaers	x	x						x
João Sabino
João Sabino
Caroline Saudoyer
Michael Schapira
Nathalie Schoofs
Nele Schoofs
Alexandra Sermeus
Francoise Smets
Michaël Somers
Dirk Staessen
Marjan Steppe
Beatrijs Strubbe							x
Jo Swinnen
Clara Thienpont
Marie Truyens
Haydeh Vafa
Stephanie Van Biervliet
Frank Van De Mierop
Gaëtan Van Den Steen
Jurgen Van Dongen
Evi Van Dyck
Andre Van Gossum
Karen Van Hoeve
Philippe Van Hootegem	x												x
Catherine Van Kemseke
Wouter Van Moerkercke		x					x				x
Steven Van Outryve
Stijn Vanden Branden	x	x					x				x
Liv Vandermeulen
Jo Vandervoort
Gigi Veereman												x
Severine Vermeire						x				x	x
Annelies Verreth
Bram Verstockt
Sophie Vieujean
Francis Weyn
Barbara Willandt

	1	2	3	4	5	6	7	8	9	10	11	12	13
	BE-SMART	CEDAR-UC	Combined therapy of biologicals and new oral drugs.	DETECT	DNA banking	GENGISCAN	HELP-AID	I-CARE	Immunization	LOVE	PACIFIC	Pediatric	SPARE
Marc Aerts
Saskia Appelmans
Morgane Barbaraci
Christel Berben
Anne Bertrand
Karin Bevers
Ann Bommerez
Anne-Marie Borremans
Layla Boutaffala
Anja Brepoels
Deborah Callebert
Nathalie Chapelier
Annick Christiaens
Lieve Coekaerts
Emilie Collet		x	x			x			x		x		x
Marie Laure Cornet
Ann D'hondt
Christine De Becker
Elien De Cock	x	x				x	x				x		x
Els De Dycker
Evva De Jonckere	x	x				x	x				x		x
Liesbet De Meuter
Jolien De rechter
Marijke De Wolf
Lien Decaesteker	x	x				x	x				x		x
Annick Deflandre
Goedele Dewitte
Christel Duchene
Isabelle Dury
Hanane El Amrite
Patricia Geens
Joline Goossens
Liesbeth Goossens
Jenny Heremans
Tine Hermans
Inge Huys
Anita Janssens
Wendy Janssens							x
Kathleen Kokke							x
Tessy Lambrechts
Melissa Lauwers
Nikki Lembrechts
Geraldine Leonard
Anita Maltère
Julie Massart
Charlotte Minsart
Lislot Mommerency
Melissa Nigro
Ariane Paps
Karine Peters
Emilie Pontus
Joke Robrechts
Nele Rooryck
Pim Sansen
Caroline Saudoyer
Martine Seegers							x
Lynn Sioncke
Larissa Staelens	x												x
Marjan Steppe
An Sterckx	x	x					x				x
Niki Strobbe
Natalia Swietec
Julie Thijs
Christella Ukunda
Ils Van de Schoot	x	x		x				x			x		x
Greet Van den Eynde
Tanja Van Dessel
Frederika Van Dyck
Nina Van Heddegem		x									x
Stephanie Van Impe
Nele Van Waes
Marie-Anne Vandebos	x	x				x	x				x		x
Sandrine Vanden Bergh
Louise Vandenbroucke	x										x		x
Sofie Vanderhasselt	x			x		x	x				x		x
Nancy Vandermeeren
Veroniek Vandewalle
Sarah Vervloesem
Valerie Wambacq
Natascha Wouters

Scientific papers

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

LIST OF PARTICIPANTS