The IBD International Genetics Consortium provides further evidence for linkage to IBD4 and shows gene-environment interaction

Marie Pierik, Huiying Yang, Michael M. Barmada, Juleen A. Cavanaugh, Vito Annese, Steven R. Brant, Judy H. Cho, Richard H. Duerr, Jean Pierre Hugot, Dermot P. McGovern, Paulina Paavola-Sakki, Graham L. Radford-Smith, P. Pavli, Mark S. Silverberg, Stephan Schreiber, Kent D. Taylor, Robert Vlietinck, H. Rodgers, N. Risch, R. EriT. Florin, E. Fowler, M. Daly, J. Rioux, H. Steinhart, P. Rutgeerts, S. Vermeire, S. Lesage, H. Zouali, T. Helio, K. Kontula, P. Paavola-Sakki, U. Turunen, P. J.P. Croucher, J. Hampe, S. Nikolaus, A. Latiano, G. Lombardi, F. Castiglione, D. Jewell, N. Lench, D. McGovern, D. Van Heel, J. E. Bailey-Wilson, A. S. Karban, C. I.M. Panhuysen, T. Moran, D. L. Nicolae, E. Swanson, Y. C. Lin, J. I. Rotter, J. P. Ackhar, R. H. Duerr, L. Zhang

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Background and Aims: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant. One gene associated with CD has been identified: NOD2/CARD15. Two independent genome-wide scans found significant evidence (logarithm of odds [LOD] 3.6) and suggestive evidence (LOD 2.8) for linkage on locus 14q11-12, also known as the IBD4 locus. To further characterize this locus, we assessed gene-enviromnent interaction (IBD4 × smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs as part of an ongoing international collaborative effort. Patients and Methods: A total of 733 IBD families, comprising 892 affected sibling pairs, were genotyped for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus. Information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location was available. Results: A significant distortion in the mean allele sharing (MAS) between affected siblings was observed for CD patients only at each of the four markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively). Maximum linkage for CD was observed at marker D14S261 (multipoint nonparametric linkage score 2.36; P ≤ 0.01; MAS 54.6%). MAS was higher in CD families in which all siblings or at least one sibling smoked compared with nonsmoking CD families (MAS, 58.90%, 57.50%, and 52.80%, respectively). Conclusions: The IBD International Genetics Consortium replicated the IBD4 locus on chromosome 14q for CD and also showed evidence for a gene-environment interaction at this locus. Further studies are needed to explore the mechanism by which smoking influences IBD4.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalInflammatory Bowel Diseases
Issue number1
StatePublished - 2005


  • Chromosome 14
  • Crohn's disease
  • Gene-environment interaction
  • Inflammatory bowel disease
  • Smoking


Dive into the research topics of 'The IBD International Genetics Consortium provides further evidence for linkage to IBD4 and shows gene-environment interaction'. Together they form a unique fingerprint.

Cite this