P1297 Family History of Inflammatory Bowel Disease: Prevalence and Its Relationship with Clinical and Genetics Factors in Patients with Ulcerative Colitis and Crohn’s Disease in a SouthAmerican Cohort
Authors: Pérez T , Bustamante M L , Reyes Perez P , Medina Rivera A , Cristobal A , Azocar-Lopez L , Segovia R , Aguilar N , Estela Petit R , Silva V , Arriagada E , De la Vega A , Matamala F , Chahuan J , Pavez-Ovalle C , Cofre C , Hernandez E , Miquel J F , Alvarez-Lobos M , Hernandez-Rocha C 
Published: January 2025

Abstract

Background
Relatives of inflammatory bowel disease (IBD) patients have a higher risk of developing the condition than the general population. Approximately 12% of IBD cases are familial. We aim to evaluate the prevalence of family history of IBD (FH-IBD) in Crohn’s disease (CD) and ulcerative colitis (UC) patients, identify clinical characteristics linked to a higher FH-IBD risk, and develop a polygenic risk score (PRS) for FH-IBD.

Methods
Patients were recruited from a Chilean IBD referral center between 2019 and 2024, yielding clinical data from 412 individuals. The FH-IBD prevalence was based on affected first-degree relatives. Clinical characteristics were compared between groups with and without FH-IBD using chi-square and Mann-Whitney U tests. Significant variables were analyzed with univariate and multivariate methods, adjusted for age, sex, diagnosis age, and smoking. A subset of 232 IBD patients was genotyped with the Illumina Infinium array, and we constructed a FH-IBD polygenic risk score from IBD risk variants in European and Asian populations.

Results
A total of 16% (67/412) had FH-IBD: 15% (15/100) in the Crohn’s disease (CD) group and 16% (52/314) in the ulcerative colitis (UC) group. In the CD group, active smoking significantly increased the risk of FH-IBD, with 18% of patients without FH-IBD reporting a history of smoking compared to 47% with FH-IBD (p = 0.03). Diagnosis age differences per the Montreal classification showed that among those without FH-IBD, 4 (5%) were A1, 50 (60%) A2, and 30 (35%) A3; while in the FH-IBD group, 4 (26.5%) were A1, 4 (26.5%) A2, and 7 (47%) A3 (p = 0.01). In the UC group, 60 of 260 patients (23%) without FH-IBD had extraintestinal manifestations, compared to 23 of 52 (44%) with FH-IBD (p = 0.004). Hospitalization history was also more common in the FH-IBD group, at 56% (29/52) versus 38% (98/260) without FH-IBD (p = 0.01). Table 1 summarizes significant risk associations between clinical variables and FH-IBD for each disease, and Figure 1 presents the PRS for FH-IBD.

Conclusion
FH-IBD prevalence was 16%, aligning with existing literature. Active smoking in CD was significantly linked to FH-IBD, unlike in UC. A CD onset age of 17 to 40 years was associated with a lower FH-IBD risk. In UC, those with FH-IBD had higher rates of extraintestinal manifestations and hospitalization. A lower median PRS was observed in the FH-IBD group, but no significant differences emerged. Recognizing these risk factors emphasizes the need for a family approach in IBD assessment, which could enhance prevention and treatment strategies. Further studies are required to validate these findings.

References
Moller FT, Andersen V, Wohlfahrt J, Jess T. Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011. Am J Gastroenterol. 2015;110(4):564-571. doi:10.1038/ajg.2015.50
Liu Z, Liu R, Gao H, et al. Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. Nat Genet. 2023;55(5):796-806. doi:10.1038/s41588-023-01384-0