Inflammatory bowel disease aggregation in Utah kindreds.

Background: The observed heritability of inflammatory bowel disease (IBD) is incompletely explained by known genetic risk factors. Kindred-specific genetic variants that cause IBD may be a source of "missing heritability." Given that they have been previously difficult to identify, we sought to identify high-risk IBD kindreds.

Methods: We used a large population-based database--the Utah Population Database (UPDB)--which contains genealogical and healthcare data to characterize the risk of Crohn's disease (CD), ulcerative colitis (UC), and IBD in kindreds. We identified CD and UC cases using ICD-9 codes. We calculated the adjusted relative risk to relatives of affected individuals. We calculated the familial standardized incidence ratio (FSIR) to quantify the kindred-specific disease risk.

Results: In all, 3601 CD cases and 3976 UC cases met inclusion criteria. A total of 655 CD kindreds and 615 UC kindreds had a statistical excess of disease. Risk of disease varied among kindreds, with some kindreds demonstrating ≈ 20-fold elevated risk. For CD, UC, and IBD, relative risks were significantly elevated for first- and second-degree relatives and first cousins. The adjusted population attributable risks for familial CD, UC, and IBD were 0.20 (95% confidence interval [CI]: 0.17-0.23); 0.17 (0.14-0.21); and 0.19 (0.17-0.22), respectively.

Conclusions: We identified multiple kindreds with a statistical excess of CD, UC, and IBD, and validated the UPDB as a resource for family studies in IBD. Given the need for novel genetic mapping strategies to explain the apparent missing heritability in IBD, further studies of these high-risk kindreds is justified.