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Am. J. Hum. Genet. 68:1165-1171, 2001

International Collaboration Provides Convincing Linkage Replication in Complex Disease through Analysis of a Large Pooled Data Set: Crohn Disease and Chromosome 16

The IBD International Genetics Consortium

abstract

Numerous familial, non-Mendelian (i.e., complex) diseases have been screened by linkage analysis for regions harboring susceptibility genes. Except for rare, high-penetrance syndromes showing Mendelian inheritance, such as BRCA1 and BRCA2, most attempts have failed to produce replicable linkage findings. For example, in multiple sclerosis and other complex diseases, there have been many reports of significant linkage, followed by numerous failures to replicate. In inflammatory bowel disease (IBD), linkage to two regions has elsewhere been reported at genomewide significance levels: the pericentromeric region on chromosome 16 (IBD1) and chromosome 12q (IBD2). As with other complex diseases, the subsequent support for these localizations has been variable. In this article, we report the results of an international collaborative effort to investigate these putative localization by pooling of data sets that do not individually provide convincing evidence for linkage to these regions.
Our results, generated by the genotyping and analysis of 12 microsatellite markers in 613 families, provide unequivocal replication of linkage for a common human disease: a Crohn disease susceptibility locus on chromosome 16 (maximum LOD score 5.79). Despite failure to replicate the previous evidence for linkage on chromosome 12, the results described herein indicate the need to further investigate the potential role of this locus in susceptibility to ulcerative colitis.
This report provides a convincing example of the collaborative approach necessary to obtain the sample numbers required to achieve statistical power in studies of complex human traits.

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
- - x x x x
Leila Amininejad x x x
Saskia Appelmans
Filip Baert x x x x x x
Thomas Billiet
Patrick Bontems
Peter Bossuyt x x x x x x
Guillaume Burnet
Peter Burvenich
Philippe Caenepeel
Olivier Cajot
Christophe Claessens x
Jean-Charles Coche
Jean-Louis Coenegrachts
Arnaud Colard x
Filip Couturier
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
Marc Etienne
Marc Ferrante x x x x x
René Fiasse
Fernand Fontaine x x
Denis Franchimont x x x x x x
Pieter Hindryckx x
Ilse Hoffman
Evelien Humblet x
Saskia Ilegems
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
Michael Schapira
Nathalie Schoofs
Nele Schoofs
Alexandra Sermeus
Francoise Smets
Michaël Somers
Dirk Staessen
Marjan Steppe
Beatrijs Strubbe x
Jo Swinnen
Clara Thienpont
Haydeh Vafa
Gert Van Assche
Stephanie Van Biervliet
Frank Van De Mierop
Gaëtan Van Den Steen
Jurgen Van Dongen
Evi Van Dyck
Andre Van Gossum
Philippe Van Hootegem x x
Catherine Van Kemseke
Wouter Van Moerkercke x x x
Steven Van Outryve
Stijn Vanden Branden x x x x
Jo Vandervoort
Gigi Veereman x
Severine Vermeire x x x
Annelies Verreth
Bram Verstockt
Francis Weyn
Barbara Willandt