P1284 Systematic evaluation of the modulation of environmental and genetic susceptibility to the development of inflammatory bowel disease by socioeconomic status

Abstract Background While the exact aetiology of inflammatory bowel disease (IBD) remains incompletely understood, it is considered to arise from a complex interplay of genetic and environmental factors. However, the contributions of these factors, particularly the role of socioeconomic status (SES), have not been fully elucidated. This study aims to systematically quantify the associations of SES, environmental and genetic susceptibility, and systemic inflammation with incident IBD, and to evaluate the potential mediating roles of environmental factors and systemic inflammation in the relationship between SES and IBD risk (Figure 1). Methods SES was derived using latent class analysis incorporating information on employment status, household income, and educational attainment. We developed an environmental risk score (ERS) from 18 key factors to quantify environmental susceptibility, and to account for the modifiability of these factors, two ERS subtypes were defined: a more modifiable ERS and a less modifiable ERS. Genetic susceptibility and systemic inflammation were assessed using a polygenic risk score and a low-grade inflammation (INFLA) score, respectively. We evaluated associations with IBD incidence using Cox proportional hazards regression models and estimated the population attributable fraction (PAF) of cases preventable under a theoretical lowest-risk scenario. Additionally, mediation analyses were conducted to explore the potential role of environmental and inflammatory factors in the SES-IBD relationship. Results During a mean follow-up of 15.9 years, 1,639 incident IBD cases were documented. We found that low SES was significantly associated with a higher risk of IBD compared to high SES (HR 1.58, 95% CI 1.36-1.84). Similar associations were observed for high ERS (HR 1.51, 95% CI 1.34-1.70), high PRS (HR 1.72, 95% CI 1.53-1.94), and high INFLA score (HR 2.09, 95% CI 1.85-2.36) when compared to the respective low score counterparts (Figure 2A). The PAF analysis indicated that 94.4% of incident IBD cases could be explained by these four combined contributions (Figure 2B). Mediation analysis indicated that 27.3% of the SES-IBD relationship was mediated by ERS (especially more modifiable ERS 18.2%) and 28.4% by INFLA score (Figure 2C). Joint analysis further demonstrated that, among participants with medium or low SES, those maintaining low ERS exposure exhibited no significant increase in IBD risk (Figure 2D). Conclusion Low SES was associated with increased risk of IBD, while adhering to low ERS may mitigate the effects of socioeconomic inequity. These findings underscore the importance of integrating socioeconomic determinants and environmental strategies into IBD prevention and clinical practice. Conflict of interest: Jing, Fangmin: No financial conflicts of interest Dan, Lintao: I have no COI related to submitted program Wang, Sidan: I disclose no relevant conflict of interest. Wellens, Judith: No conflicts Yao, Jialu: No conflict of interest Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Wang, Xiaoyan: I have no conflict of interest to disclosure. Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Li, Xue: No conflict of interest Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Dr. Chen, Jie: No conflict of interest