Genetics of kidney failure and the evolving story of APOL1
David J. Friedman, Martin R. Pollak
David J. Friedman, Martin R. Pollak
Published September 1, 2011
Citation Information: J Clin Invest. 2011;121(9):3367-3374. https://doi.org/10.1172/JCI46263.
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Genetics of kidney failure and the evolving story of APOL1

Abstract

Chronic kidney disease (CKD) results from a wide array of processes that impair the kidney’s ability to perform its major functions. As many as 20 million Americans suffer from CKD and nearly a half million from end-stage renal disease, but there are also examples of centenarians with adequate renal function. Family-based and genome-wide studies suggest that genetic differences substantially influence an individual’s lifetime risk for kidney disease. One emerging theme is that evolution of genes related to host defense against pathogens may limit kidney longevity. The identification of these genetic factors will be critical for expanding our understanding of renal development and function as well as for the design of novel therapeutics for kidney disease.

Authors

David J. Friedman, Martin R. Pollak

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Figure 3

Effect size versus allele frequency.

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Effect size versus allele frequency. For genetic variants influencing hu...
For genetic variants influencing human traits, effect size tends to vary inversely with allele frequency. As a rule, Mendelian diseases are caused by extremely rare variants (including unique mutations) with very large effect size (~1,000-fold), whereas most analyses of complex traits to date by GWAS have led to the identification of common genetic variants with individually small effect (typically less than 2-fold; in most reports to date, just slightly above 1). In contrast, variants on which recent positive selection has been acting may become more common than expected and still have large effect size. The disorders caused by mutations in HBB (such as sickle cell disease) and APOL1-associated kidney disease are examples of this phenomenon.