Abstract Background 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 (i.e., 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 (Table 1). The proband concordance rate for Crohn’s disease was 0.30 in monozygotic pairs and 0.02 in dizygotic pairs (Table 2). 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. Conflict of interest: Grännö, Olle: No conflict of interest Thunberg, Joel: No conflict of interest Ludvigsson, Jonas: Jonas F. Ludvigsson has coordinated a study on behalf of the Swedish IBD quality register (SWIBREG). That study received funding from the Janssen corporation. Ludvigsson has also received funding from Takeda for celiac disease research and from Merck on unrelated IBD research and to develop a paper reviewing national healthcare registers in China. Kuja-Halkola, Ralf: No conflict of interest Lindqvist, Carl Mårten: No conflict of interest Halfvarson, Jonas: Grant support: Swedish Foundation for Strategic Research (RB13-0160 to J.H.), the Swedish Research Council (2020-02021 to J.H.), the Örebro University Hospital research foundation (OLL-890291 to J.H.), NordForsk (90569 to J.H.) and Vinnova (2019-01185 to JH and 2024-01155 co-applicant), IHI, EU, INTERCEPT (Grant agreement number 101194780, co-applicant), miGut-Health, HORIZON-HLTH-2022, EU (Grant Agreement 101095470, Co-applicant), 3TR, IMI 2, EU, (Grant agreement number 831434, Co-applicant), Janssen, MSD, and Takeda. Consulting and/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Hospira, Index Pharmaceuticals, Janssen, Johnson & Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB and speaker’s fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma and research grant support from Janssen, Merck Sharp & Dohme and Takeda.
Grännö et al. (Thu,) studied this question.
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