Pos0871 Heritability and Phenotypic Variation of Sarcoidosis in the Icelandic Population

Background: Studies on the etiology of sarcoidosis have shown contradictory results. It is generally accepted that the immune system of a genetically susceptible individual gets triggered by an unknown antigen, leading to granuloma formation in various organs. Objectives: The present study maps the pattern of familial distribution of all known, biopsy-verified sarcoidosis diagnoses made in a nationwide Icelandic population from 1981 till the end of 2021. Methods: All cases were re-confirmed and categorized into one of the five phenotypic groups described by Schupp et al. (2018). Distant relationships were accurately traced for relatives of sarcoidosis patients and their mates using the Icelandic Genealogy Database. This allows the creating of matched control groups as needed to calculate Relative Risk (RR), the Kinship Coefficient (KC), and their statistical significance. Results: In the study period, there were 462 patients with biopsy-proven diagnoses of sarcoidosis. We identified 282 extended families and seven sibling pairs with sarcoidosis. Twenty families had five or more affected individuals. RR was 3.7 (95% CI: 1.54,8.55) in 1st-degree relatives (P=0.003), 1.65 (95% CI: 1.05,1.92) in 4th-degree relatives, (P=0.014) and 1.57 (95% CI: 1.08,1.70) in 5th-degree relatives (P=0.003). RRs among 1st-5th-degree relatives of the patients' mates were not significant. KC for sarcoidosis was low and significant only for the first two meiosis (KC=1.06, P<0.008 and KC=1.01, P=0.011, respectively). The most common sarcoidosis phenotypes were pulmonary (47.6%), ocular-cardiac-cutaneous and central nervous system (OCCC) (21.6%), and musculoskeletal cutaneous (MSC) (20.9%) sarcoidosis. There was no clustering of a single phenotype in the extended sarcoidosis families. Conclusion: Heredity is not a strong risk factor in our study population. The risk is strongest for 1st generation relatives of patients, and single phenotypes do not cluster in distinct families. The study provides important clinical information for treating physicians and contributes to understanding the etiology of the disease. REFERENCES: [1] Schupp JC, Freitag-Wolf S, Müller-Quernheim J. Phenotypes of organ involvement in sarcoidosis. Eur Respir J. 2018 Jan 25;51(1):1700991. Acknowledgements: NIL. Disclosure of Interests: None declared.