Journal Article

Single nucleotide polymorphisms in <i>TNFSF15</i> confer susceptibility to Crohn's disease

Keiko Yamazaki, Dermot McGovern, Jiannis Ragoussis, Marta Paolucci, Helen Butler, Derek Jewell, Lon Cardon, Masakazu Takazoe, Torao Tanaka, Toshiki Ichimori, Susumu Saito, Akihiro Sekine, Aritoshi Iida, Atsushi Takahashi, Tatsuhiko Tsunoda, Mark Lathrop and Yusuke Nakamura

in Human Molecular Genetics

Volume 14, issue 22, pages 3499-3506
Published in print November 2005 | ISSN: 0964-6906
Published online October 2005 | e-ISSN: 1460-2083 | DOI:

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The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80 000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P=1.71×10−14 with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations.

Journal Article.  5867 words.  Illustrated.

Subjects: Genetics and Genomics

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