J Crohns Colitis. 2022 Aug 9;jjac111. doi: 10.1093/ecco-jcc/jjac111. Online ahead of print.

Joana Torres ^1 2 3, Catarina Gomes ¹, Camilla Jensen ⁴, Manasi Agrawal ^3 5, Francisco Morão ^6 7, Tine Jess ^5 8, Jean-Frédéric Colombel ³, Kristine H Allin ⁵, Johan Burisch ^9 10

Author information

¹Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal.

²Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal.

³The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY.

⁴Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

⁵Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

⁶Pediatrics Department, Centro Materno Infantil do Norte - Centro Hospitalar e Universitário do Porto, Porto, Portugal.

⁷Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.

⁸Department of Epidemiology Research, Statens Serum Institut, Copenhagen S, Denmark.

⁹Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.

¹⁰Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark.

Abstract

Introduction: A family history of IBD is the strongest risk factor for disease. However, some first-degree relatives (FDRs) will develop disease, while others will not.

Methods: Using the nationwide Danish National Patient Register, we examined risk factors in families with ≥2 affected FDRs. First, we compared exposures between siblings with and without IBD within the same family (within family analysis). Second, we compared exposures between individuals with and without IBD across all families (across family analysis). Exposures included sex, birth order, mode of delivery, antibiotics, personal and family history of immune-mediated diseases, gastrointestinal infections, and surgical history preceding diagnosis. Uni- and multivariable conditional logistic regression analyses were conducted.

Results: In the "within family analysis", 1669 families were included (1,732 cases, 2,447 controls). Female sex (adjusted odds ratio (aOR): 1.40, 95% CI 1.23, 1.59), history of ankylosing spondylitis (aOR: 2.88, 95% CI 1.05, 7.91) and exposure to antibiotics (aOR: 1.28, 95% CI 1.02, 1.61), increased the risk for IBD. In the "across family analysis", 1,254 cases and 37,584 controls were included, confirming association with prior ankylosing spondylitis (aOR: 3.92, 95% CI 1.38, 11.12), and exposure to antibiotics (aOR: 1.29, 95% CI 1.04, 1.60). Having ≥2 relatives (aOR: 6.26, 95% CI 1.34, 29.29) or a sibling with IBD (aOR: 1.36, 95% CI 1.18, 1.57), increased the risk of IBD. Appendectomy reduced the risk of UC (aOR: 0.32, 95% CI 0.14, 0.72).

Conclusion: In families with IBD, we identified risk factors for the unaffected FDR to develop disease. These findings provide an opportunity for counselling IBD relatives.