Heterogeneity of familial risk in sarcoidosis.

Familial clustering of sarcoidosis and the higher prevalence and clinical severity of sarcoidosis in African Americans suggests etiologic heterogeneity. To test for heterogeneity in familial risk of sarcoidosis, we studied 3,395 siblings and parents of 558 index cases (361 African American, 197 Caucasian) diagnosed at Henry Ford Hospital between 1951 and 1994. Using the age- and sex-specific cumulative incidence of sarcoidosis in our sample, we found a statistically significant heterogeneity in familial risk of disease (P < .001). To determine if this was due to a greater risk of sarcoidosis in African Americans, we recalculated disease probabilities using age-, sex-, and race-specific disease cumulative incidence and found the same amount of heterogeneity in familial risk (P < .001). Index cases (n = 69) from high-risk families were more likely to be African American (odds ratio [OR] = 3.24; 95% confidence interval (CI) = 1.71-6.14) and to have an offspring or second- degree relative affected (OR = 6.21; 95% CI = 2.86-13.45). We conclude that the heterogeneity of familial sarcoidosis risk found in this study is supportive of multiple etiologies. Our results also show that a quantitative assessment of familial risk based on siblings and parents may be a useful screening tool for identifying families with additional affected members. Of the high-risk families, African Americans made up a greater-than-expected percentage even after accounting for differences in disease prevalence. We suggest targeting African Americans for studies of sarcoidosis that focus on Mendelian hypotheses and genetic linkage.