Familial risks for gallstones in the population of Sweden

Objectives Gallstone disease (cholelithiasis) has a familial component, but detailed data on the modification of familial risk are lacking. Using nationwide hospital and population records, we aimed to determine detailed familial risks for medically diagnosed gallstone disease. Design Subjects were obtained from the Multigeneration Register, which contains family data on the Swedish population, and patients with gallstone disease were identified from the Hospital Discharge Register (1964-2015) and the Outpatient Register (2001-2015). Standardised incidence ratios (SIRs) were calculated as the ratio of observed to expected number of cases. Results Gallstone disease was diagnosed in 660 732 patients, with an overall incidence of 131 per 100 000 person-years. Familial cases accounted for 36.0% of all patients with gallstone disease. Of these, 50.9% had a parental family history (SIR 1.62), 35.1% had a sibling history (SIR 1.75) and 14.0% had a parental+sibling history (SIR 2.58). Among a total of 54 630 affected siblings, 84.4% were sibling pairs (SIR 1.55). However, the remaining 15.6% of the affected siblings constituted the high-risk group of multiple affected siblings and an SIR >10; these persons accounted for 7.7% of all familial cases. The spousal risk was only slightly increased to 1.18. Conclusions Overall, the results point to the underlying genetic causes for the observed familial clustering, which may involve polygenic gene-environmental interactions for most familial cases but high-risk genes in close to 10% of cases. Family histories should be taken into account in the medical setting and used for counselling of at-risk individuals.