Whole genome sequencing identifies variants associated with sarcoidosis in a family with a high prevalence of sarcoidosis

OBJECTIVE: We studied genetic risk factors associated with sarcoidosis within a family with a high prevalence of this disease. METHODS: We studied 41 members of a family with a high rate of sarcoidosis, including an index patient with treatment-resistant neurosarcoidosis. Whole genome sequencing was performed for six affected family members and variations associated with loss of function were filtered out as candidate genes. Findings were validated by using amplicon sequencing within all 41 family members with DNA available and candidate genes were screened on absence and presence within the sarcoidosis affected and non-affected. RESULTS: Family members (n = 61) from 5 generations were available for participation including 13 subjects diagnosed with sarcoidosis (20%). Analyses identified 36 candidate variants within 34 candidate genes. Variations within three of these genes (JAK2, BACH2, and NCF1) previously have been associated with autoimmune diseases. CONCLUSIONS: We identified 34 genes with a possible role in the etiology of sarcoidosis, including JAK2. Our results may suggest evaluation of JAK inhibitors in treatment-resistant sarcoidosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10067-021-05684-w.