OBJECTIVES:Familial risk estimates are useful for genetic counseling, etiological understanding, and design of gene identification studies. We wanted to estimate the associations of ulcerative colitis (UC) and Crohn's disease (CD) with 32 autoimmune and related diseases among parents and offspring, singleton siblings, twins, and spouses.METHODS:The Multigeneration Register in Sweden provides reliable access to information on families among 11.5 million individuals throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated as relative risks for UC/CD in family members of patients diagnosed with any of the 34 diseases compared with those lacking affected family members through years 1964-2004.RESULTS:Among a total of 441,642 patients diagnosed with autoimmune and related conditions, 25,846 were diagnosed with UC and 18,885 with CD. Familial cases amounted to 5.4% of all UC patients and 6.5% of CD patients. SIR for UC was 3.9 (95% confidence interval 3.5-4.3) in offspring of affected parents, 4.6 (3.0-7.4) in siblings, 10.4 (6.5-15.8) in families of affected parents and siblings, and 6.3 (1.9-17.7) for monozygotic twins. The respective SIRs for CD were 6.0 (5.4-6.7), 6.3 (4.1-9.8), 34.0 (24.9-45.3), and 23.4 (10.1-51.1). All discordant associations, i.e., those between CD and other diseases, were also found for UC, including ankylosing spondylitis, asthma, polymyalgia rheumatica, psoriasis, and sarcoidosis. For UC, six additional associations were observed. No correlations between specific diseases were found among spouses, but between UC or CD and any disease it was 1.1 (1.0-1.1).CONCLUSIONS:The concordant familial risks for UC and CD were lower than those commonly cited. Both diseases are associated with several autoimmune and related diseases, suggesting genetic sharing.Am J Gastroenterol advance online publication, 25 August 2009; doi:10.1038/ajg.2009.496.