Abstract
BACKGROUND AND AIMS: Limited statistical power has hampered previous estimates of concordance between relatives and heritability in inflammatory bowel diseases (IBD). To examine the genetic component of Crohn's disease and ulcerative colitis, we established the largest nationwide IBD twin cohort to date and assessed estimates of concordance and heritability. METHODS: We used the Swedish Twin Registry to identify all twins from complete pairs with known zygosity born between 1886 and 2004. The Swedish National Patient Register was used to identify all patients diagnosed with IBD. We calculated proband concordance rates and fitted a model estimating explained variance in diseases due to genetics (ie, the heritability), environment shared between twins, and environment unique to each twin. RESULTS: A cohort of 111 080 twins was followed until a median age of 62.2 years, during which 964 individuals were diagnosed with IBD. The proband concordance rate for Crohn's disease was 0.30 in monozygotic pairs and 0.02 in dizygotic pairs. The corresponding rates for ulcerative colitis were 0.15 and 0.03. After adjusting for sex and birth year, heritability was estimated to be 0.78 (95% CI: 0.68-0.87) for Crohn's disease and 0.57 (95% CI: 0.46-0.69) for ulcerative colitis. CONCLUSION: In this large population-based twin study, the heritability of Crohn's disease was 0.78 and 0.57 for ulcerative colitis. These findings highlight the disparity between heritability estimates from twin studies and those inferred from genome-wide association studies, underscoring the need for continued exploration of the genetic basis of IBD.