  MYH9 has been proposed as a major genetic risk locus for a spectrum of
non-diabetic end stage kidney disease (ESKD). We use recently released
sequences from the 1000 Genomes Project to identify two western African
specific missense mutations (S342G and I384M) in the neighbouring APOL1 gene,
and demonstrate that these are more strongly associated with ESKD than
previously reported MYH9 variants. We also show that the distribution of these
risk variants in African populations is consistent with the pattern of African
ancestry ESKD risk previously attributed to the MYH9 gene. Additional
associations were also found among other members of the APOL gene family, and
we propose that ESKD risk is caused by western African variants in members of
the APOL gene family, which evolved to confer protection against pathogens,
such as Trypanosoma.
