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. Key Points• JAK2 has a potential role in the etiology of sarcoidosis and is a potential therapeutic target.• We identified 33 additional candidate genes of which BACH2 and NCF1 have been previously associated with autoimmune disease.