Familial risk and phenotypic variation of sarcoidosis in the Icelandic population.

BACKGROUND

The familial risk of sarcoidosis is heterogeneous, and previous studies demonstrate conflicting results. The present study maps the pattern of familial distribution of all known, biopsy-verified sarcoidosis in the Icelandic population (1981-2021).

METHODS

All cases were re-confirmed and categorised into one of the five phenotypic groups described by Schupp , and in different groups based on disease severity. Distant relationships were accurately traced for relatives of sarcoidosis patients and their mates using the nationwide Icelandic Genealogy Database. This allows creation of matched control groups for the calculation of relative risk and kinship coefficient (KC).

RESULTS

462 patients with biopsy-proven diagnoses of sarcoidosis were included. We identified 282 extended families and seven sibling pairs with sarcoidosis. 20 families had five or more affected individuals. Relative risk (RR) was 3.7 (95% CI 1.54-8.55) in 1st-degree relatives (p=0.003), 1.65 (1.05-1.92) in 4th-degree relatives (p=0.014) and 1.57 (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 only significant for the first two meioses (KC=1.06, p<0.008 and KC=1.01, p=0.011, respectively). The most common sarcoidosis phenotypes were pulmonary-lymphonodal (47.6%), ocular-cardiac-cutaneous and central nervous system (21.6%), and musculoskeletal cutaneous (20.9%). There seems to be no clustering of a single phenotype or resistant sarcoidosis in the extended sarcoidosis families.

CONCLUSION

Our study does not consider heritability a strong risk factor for sarcoidosis. The risk is highest for 1st-degree relatives of patients with sarcoidosis. Single phenotypes and resistant sarcoidosis do not cluster in distinct families.