Nature 379, 821 - 823 (29 February 1996); doi:10.1038/379821a0

Mapping of a susceptibility locus for Crohn's disease on chromosome 16

Jean-Pierre Hugot^*, Pierre Laurent-Puig^*, Corine Gower-Rousseau^†, Jane M. Olson^‡, John C. Lee^§, Laurent Beaugerie, Isam Naom^¶, Jean-Louis Dupas^£, André Van Gossum, Marianne Orholm^††, Catherine Bonaiti-Pellie^‡‡, Jean Weissenbach^§§, Christopher G. Mathew^¶, John E. Lennard-Jones^§, Antoine Cortot^†, Jean-Frédéric Colombel^† & Gilles Thomas^*

^* Laboratoire de Génétique des Tumeurs, INSERM U 434, Institut Curie, 75231 Paris, France
^† Registre des Maladies Inflammatoires du Tube Digestif du Nord-Ouest de la France, CHRU, 59037 Lille, France
^‡ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44109, USA
^§ St Mark's Hospital, London EC1V 2PS, UK
Service de Gastro-Entérologie et d'Hépatologie, Hôpital Rothschild, 75571 Paris, France
^¶ Division of Medical and Molecular Genetics, UMDS Guy's & St Thomas's Hospitals, London SE1 9RT, UK
^£ Service d'Hépato-Gastro-Entérologie, Hopital Nord, 80054 Amiens, France
Service de Gastro-Entérologie et d'Hépato-Pancréatologie, Hopital Erasme, 1070 Bruxelles, Belgium
^** GETAID: Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives, 33 blvd de Picpus, 75012 Paris, France
^†† Department of Medical Gastroenterology, Herlev Hospital, Copenhagen, Denmark
^‡‡ Unité d'Epidémiologie des Cancers, Institut Gustave Roussy, 94805 Villejuif, France
^§§ CNRS URA 1922 Généthon, 1 rue de I'Internationale, 91002 Evry, France
To whom correspondence should be addressed.

CROHN'S disease (CD) and ulcerative colitis are the major forms of chronic inflammatory bowel diseases in the western world, and occur in young adults with an estimated prevalence of more than one per thousand inhabitants¹. The causes of inflammatory bowel diseases remain unknown, but genetic epidemiology studies^2–5 suggest that inherited factors may contribute in part to variation in individual susceptibility to Crohn's disease. A genome-wide search performed on two consecutive and independent panels of families with multiple affected members, using a non-parametric two-point sibling-pair linkage method, identified a putative CD-susceptibility locus on chromosome 16 (P < 0.01 for each panel). The localization was centred around loci D16S409 and D16S419 by using multipoint sibpair analysis (ref. 6, and J.M.O., manuscript submitted) (P < 1.5 x 10^-5). This region of the genome contains candidate genes which may be relevant to the pathogenic mechanism of inflammatory bowel diseases.

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