Risk of irritable bowel syndrome in first-degree, second-degree and thirddegree relatives of affected individuals: a nationwide family study in Sweden

Objectives IBS aggregates in families, but the familial risk of IBS has only been determined in first-degree relatives and spouses. This nationwide study aimed to determine the familial risk of IBS in first-degree, second-degree, and third-degree relatives and spouses of affected individuals in order to estimate the relative influences of genes and shared family environment. Methods We performed a case-cohort study. The Swedish Multigeneration Register was linked to the Hospital Discharge Register for the period 1987-2010 and the Swedish Outpatient Care Register for 2001-2010. ORs for IBS were calculated for relatives of individuals who had been diagnosed with IBS compared with relatives of individuals unaffected by IBS as the reference group. ORs were also determined for IBS cases diagnosed in primary healthcare in four Swedish counties (2001-2007). Results The ORs for IBS were 1.75 in siblings (95% CI 1.63 to 1.89), 1.82 in offspring (1.67 to 1.97), 1.90 in parents (1.76 to 2.05), 1.10 in maternal half-siblings (0.88 to 1.39), 1.78 in paternal half-siblings (1.48 to 2.15), 1.27 in nieces/nephews (1.18 to 1.38), 1.11 in cousins (1.04 to 1.18), and 1.51 in spouses (1.24 to 1.84) of probands diagnosed with IBS. The OR for probands diagnosed in primary healthcare was 1.82 in siblings (1.52 to 2.18), and 1.82 in offspring (1.49 to 2.21). Conclusions The increased IBS risk among first-degree relatives and also second-degree and third-degree relatives indicates a genetic component of the familial clustering of IBS. However, a non-genetic contribution is also suggested by the increased risk among spouses.