IgA nephropathy, the most common cause of glomerulonephritis, is linked to6q22-23

End-stage renal disease (ESRD) is a major public: health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialys is treatment(1,2). IgA nephropathy (IgAN) is the most common form of glomer ulonephritis, a principal cause of ESRD worldwide(1,2); it affects up to 1. 3% of the population(3-6) and its pathogenesis Is unknown. Kidneys of peopl e with IgAN show deposits of IgA-containing immune complexes with prolifera tion of the glomerular mesangium (Fig. 1). Typical clinical features includ e onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure(6-9). Althoug h not generally considered a hereditary disease, striking ethnic variation in prevalence(1-6,10) and familial clustering(11-16), along with subclinica l renal abnormalities among relatives of IgAN cases(9,14-16), have suggeste d a heretofore undefined genetic component. By genome-wide analysis of link age in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-2 3 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.