APOL1 variants and kidney disease in people of recent African ancestry

Stanley Center, Broad Institute, Cambridge, MA 02142, USA.
Nature Reviews Nephrology (Impact Factor: 8.54). 02/2013; 9(4). DOI: 10.1038/nrneph.2013.34
Source: PubMed


Coding variants within the APOL1 gene have been associated with kidney disease, explaining an association that was previously attributed to variants within the neighbouring MYH9 gene. To better define the role of APOL1 in causing kidney disease in individuals of African ancestry, we performed an extensive survey of the common variation in the region surrounding the APOL1 gene, as seen through the lens of the 1000 Genomes Project. Arguing by exclusion, it is reasonable to conclude that the putative APOL1 causal variants are not proxies for any other variants with more direct roles in kidney disease. Our statistical argument is in part made possible by the exceptionally young age of the APOL1 coding variants coupled with the unusually high rate of genetic recombination surrounding this gene. Although no biological evidence currently exists for the causality of APOL1 variants with kidney disease, our statistical reasoning provides a strong case for causality, and a region to target in future functional studies.

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    • "Cumulative evidence over many years have demonstrated that African Americans (AAs) develop 4–5 fold higher rates of diverse forms of progressive kidney disease, including focal segmental glomerulosclerosis (FSGS), HIVAN, and hypertension-attributed end stage kidney disease (ESKD), compared with European Americans (EAs) (Tzur et al., 2010; Kopp et al., 2011; Quaggin and George, 2011; Genovese et al., 2013; Kasembeli et al., 2015). In several forms of nephropathy, this disparity reaches a greater than 10-fold difference. "
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