DOI: 10.1073/pnas.95.13.7502. Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and <i>IBD1</i>

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1

10.1073/pnas.95.13.7502

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The idiopathic inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 × 10 −4 ), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 × 10 −5 ), and at chromosome 1p (MLod = 2.65, P = 2.4 × 10 −4 ) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 × 10 −4 ), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1 , in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 × 10 −3 ), particularly among Ashkenazim (MLod = 1.51, P = 7.8 × 10 −3 ); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.

Bibliography

Cho, J. H., Nicolae, D. L., Gold, L. H., Fields, C. T., LaBuda, M. C., Rohal, P. M., Pickles, M. R., Qin, L., Fu, Y., Mann, J. S., Kirschner, B. S., Jabs, E. W., Weber, J., Hanauer, S. B., Bayless, T. M., & Brant, S. R. (1998). Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1. Proceedings of the National Academy of Sciences, 95(13), 7502â7507.

Authors 16

Judy H. Cho (first)
Dan L. Nicolae (additional)
Leslee H. Gold (additional)
Carter T. Fields (additional)
Michele C. LaBuda (additional)
Patrick M. Rohal (additional)
Michael R. Pickles (additional)
Li Qin (additional)
Yifan Fu (additional)
Jasdeep S. Mann (additional)
Barbara S. Kirschner (additional)
Ethylin Wang Jabs (additional)
James Weber (additional)
Stephen B. Hanauer (additional)
Theodore M. Bayless (additional)
Steven R. Brant (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:59 p.m.)
Indexed	2 months ago (June 27, 2025, 9:44 a.m.)
Issued	27 years, 2 months ago (June 23, 1998)
Published	27 years, 2 months ago (June 23, 1998)
Published Online	27 years, 2 months ago (June 23, 1998)
Published Print	27 years, 2 months ago (June 23, 1998)

Funders 0

None

BibTeX

@article{Cho_1998, title={Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.13.7502}, DOI={10.1073/pnas.95.13.7502}, number={13}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Cho, Judy H. and Nicolae, Dan L. and Gold, Leslee H. and Fields, Carter T. and LaBuda, Michele C. and Rohal, Patrick M. and Pickles, Michael R. and Qin, Li and Fu, Yifan and Mann, Jasdeep S. and Kirschner, Barbara S. and Jabs, Ethylin Wang and Weber, James and Hanauer, Stephen B. and Bayless, Theodore M. and Brant, Steven R.}, year={1998}, month=jun, pages={7502–7507} }

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