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Genetics of kidney failure and the evolving story of APOL1
David J. Friedman, Martin R. Pollak
Published in Volume 121, Issue 9
J Clin Invest. 2011; 121(9):3367–3374 doi:10.1172/JCI46263
This article Copyright © 2011, The American Society for Clinical Investigation
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Figure 3
Effect size versus allele frequency.

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.

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