Our analysis shows that the association between the chromosome 22 locus and FSGS risk is due to a genetic variant or variants that are likely to have arisen relatively recently in the African population. This region spans the APOL1 and MYH9 genes. Recent literature suggests recent selective pressure in Africa on the APOL1 locus, due to Trypanosoma brucei rhodesiense, a subclade of Trypanosoma brucei which recently adapted to be able to affect human hosts [16]. This selective pressure would explain why this long haplotype has attained high frequency in people of African descent, and makes APOL1 a good candidate for explaining the four fold increase of in FSGS in African Americans. This also raises the distinct possibility that a disease-influencing alteration in MYH9 was brought to high frequency because of linkage with APOL1.
