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Nature Genetics, January 2011, Volume 43, Number 1

Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease

Yukihide Momozawa, Myriam Mni, Kayo Nakamura, Wouter Coppieters, Sven Almer, Leila Amininejad, Isabelle Cleynen, Jean-Frédéric Colombel, Peter de Rijk, Olivier Dewit, Yigael Finkel, Miquel A Gassull, Dirk Goossens, Debby Laukens, Marc Lémann, Cécile Libioulle, Colm O'Morain, Catherine Reenaers, Paul Rutgeerts, Curt Tysk, Diana Zelenika, Mark Lathrop, Jurgen Del-Favero, Jean-Pierre Hugot, Martine de Vos, Denis Franchimont, Severine Vermeire, Edouard Louis & Michel Georges

abstract

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn’s disease1,2. However, common disease-associated SNPs explain at most ~20% of the genetic variance for Crohn’s disease. Several factors may account for this unexplained heritability3–5, including rare risk variants not adequately tagged thus far in GWAS6–8. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer9, plasma high-density lipoprotein cholesterol levels10, blood pressure11, type 1 diabetes12, hypertriglyceridemia13 and, in the case of Crohn’s disease, for NOD2 (refs. 14,15).
Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn’s disease in 63 GWAS-identified positional candidate genes.
 
We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn’s disease.

LIST OF PARTICIPANTS

Legend:       Coordinating PI     Participants

1. BE-SMART | 2. CEDAR-UC | 3. COMBINED THERAPY OF BIOLOGICALS AND NEW ORAL DRUGS. | 4. DETECT | 5. DNA BANKING | 6. GENGISCAN | 7. HELP-AID | 8. I-CARE | 9. IMMUNIZATION | 10. LOVE | 11. PACIFIC | 12. PEDIATRIC | 13. SPARE
1 2 3 4 5 6 7 8 9 10 11 12 13
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
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