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.
Guthery
Stephen L
SL
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah 84113, USA. Stephen.Guthery@hsc.utah.edu
Mineau
Geraldine
G
Pimentel
Richard
R
Williams
Marc S
MS
Kerber
Richard A
RA
D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology* / Q000235:genetics; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014589:Utah / Q000453:epidemiology