The strongest correlations found were that the second sibling with sarcoidosis was three times more likely to have ocular or liver involvement if the first sibling had involvement of these organs. However, the concordance of these phenotypes was relatively weak. In addition, there was virtually no concordance between the members of sibling pairs in terms of clinical course.
Our approach in analyzing phenotypic expression of a disease in sibling pairs was not unique. A similar approach as been used to examine disease similarity in sibling pairs with multiple sclerosis and rheumatoid arthritis. Trojano and colleagues found that sibling pairs with multiple sclerosis were more likely than unrelated patients to have a similar age of onset, progression of disease, and sensory symptoms. However these investigators could not identify a genetic explanation for these phenotypic differences. Silman et al failed to find a greater concordance of rheumatoid arthritis phenotypes within families than between them.
We separated full-sibling pairs and half siblings in our analysis because we suspected that stronger associations would be found between full siblings, since full-sibling pairs share twice as many genes as do half-sibling pairs and could be more likely to share environmental exposures. In both full-sibling and half-sibling pairs, sarcoidosis was diagnosed in the younger sibling at an age approximately 3 years earlier than the older sibling. One possible explanation is that the younger sibling and his/her physician were attuned to the possibility of sarcoidosis after the older sibling had acquired the disease. However, this statistically significant difference in age at diagnosis showed an extremely weak correlation between the siblings (R2 = 0.09 and R2 = 0.11 for the full-sibling and half-sibling pairs and full-sibling pairs, respectively). No significant differences in baseline spirometry, chest radiograph, or number of organs involved were found between members of sibling pairs. Of the 15 organ systems examined in full-sibling pairs, only eye involvement was statistically more likely in both siblings than by chance alone, but the level of agreement was poor. When the full-sibling and half-sibling pairs were analyzed together in a logistic regression model, we found a statistically significant threefold increased risk of liver or ocular involvement for the second sibling if the first member of the pair had involvement of one of these organs.