Sex differences in coeliac disease risk: a Swedish sibling design study

Background: For unknown reasons girls are at an increased risk of coeliac disease compared to boys. However, the observed association might be confounded, since maternal coeliac disease is associated with both an increased risk of the disease in first-degree relatives as well as an increased ratio of girls to boys in offspring.

Aims: We investigate the effect of sex on the risk of coeliac disease before the age of two years using sibling design.

Methods: We identified all singleton children (n=792,401) born between 1987 and 1993 in Sweden using the Swedish Medical Birth Registry. Coeliac disease cases (2264) were identified using the Swedish National Inpatient Registry. We applied both conventional population-based Cox regression models and sibling designs modelling the association in sex discordant siblings.

Results: We observed a conclusively increased risk of coeliac disease in girls compared to boys, using both sibling design (hazard ratio 1.67, 95% confidence interval 1.44-1.93) and conventional Cox regression analysis (hazard ratio 1.75, 95% confidence interval 1.61-1.91) that could not be explained by perinatal factors previously associated with the disease.

Conclusions: We confirm that female sex is causally associated with childhood coeliac disease, but the reasons remains unknown.