HETEROGENEITY OF FAMILIAL RISK IN SARCOIDOSIS

Familial clustering of sarcoidosis and the higher prevalence and clini cal severity of sarcoidosis in African Americans suggests etiologic he terogeneity. To test for heterogeneity in familial risk of sarcoidosis , we studied 3,395 siblings and parents of 558 index cases (361 Africa n American, 197 Caucasian) diagnosed at Henry Ford Hospital between 19 51 and 1994. Using the age- and sex-specific cumulative incidence of s arcoidosis in our sample, we found a statistically significant heterog eneity in familial risk of disease (P < .001). To determine if this wa s due to a greater risk of sarcoidosis in African Americans, we recalc ulated disease probabilities using age-, sex-, and race-specific disea se 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 seco nd-degree relative affected (OR = 6.21; 95% CI = 2.86-13.45). We concl ude 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 pare nts may be a useful screening tool for identifying families with addit ional affected members. Of the high-risk families, African Americans m ade up a greater-than-expected percentage even after accounting for di fferences in disease prevalence. We suggest targeting African American s for studies of sarcoidosis that focus on Mendelian hypotheses and ge netic linkage. (C) 1996 Wiley-Liss, Inc.