In order to determine which SNPs associate with disease, rather than associate with ancestry, we performed a controlled analysis of a 1000kb region on chromosome 22 from position 34,500kb to position 35,500kb (NCBI36.3 coordinates). Using the Hidden Markov Model (HMM) described in the Methods, we identified 54 cases and 1141 controls whose two chromosomes are both of African ancestry in this same 1000kb region. As we expected, most of the SNPs that previously associated with FSGS were shown to be artifacts of ancestry alone. Importantly, we found many previously unidentified SNPs that associated strongly with FSGS over many linkage disequilibrium blocks. These blocks include genes APOL1, APOL2, APOL4, as well as MYH9. By investigating the patterns of linkage disequilibrium in this 1000kb region from the African Yoruba Hapmap participants [20], we conclude that the disease causing variant is likely contained in a long 60kb region (NCBI36.3 chromosome 22 position 34,982,110–35,044,581 defined by SNPs rs7284919 and rs2239784 which contains part of APOL1 as well as part of MYH9) which spans several different linkage disequilibrium blocks. In Table 2 we show results for those SNPs which associated after ancestry correction with a p-value p<10−5, and for haplotype E-1p and T-1.
