Results from a genome-wide search for predisposing genes in sarcoidosis

Sarcoidosis is a systemic disease of granulomatous inflammation and unknown etiology. An inherited predisposition is involved, and many candidate susc eptibility genes have been tested in association studies. We have applied t he more general strategy of genome-wide microsatellite linkage analysis to identify chromosomal regions that contribute to the risk of sarcoidosis. On the basis of 225 microsatellite markers tested in 63 families with affecte d siblings (138 patients) and multipoint nonparametric linkage (NPL) analys is, we found the most prominent peak (six adjacent markers including D6S166 6; NPL score = 2.99; p = 0.001) at the major histocompatibility complex (MH C). Six minor peaks (p < 0.05) were found on chromosomes 1 (D1S1665), 3 (D3 S1766), 7 (D7S821 and D7S3070), 9 (D9S934), and the X chromosome (DXS6789). A subset of nine families with more than two affected siblings (30 patient s) contributed little to the peak at the MHC (D6S1666, NPL score = 0.79; p = 0.21). Our results point to locus heterogeneity of susceptibility to sarc oidosis, with a major effect of the MHC.