Chronic kidney disease (CKD) is an increasing concern in the United States due to its rapidly rising prevalence, particularly among African Americans. Epigenetic DNA methylation markers are becoming important biomarkers of chronic diseases such as CKD. To better understand how these methylation markers play a role in kidney function, we measured 26,428 DNA methylation sites in 972 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We then evaluated (1) whether epigenetic markers are associated with estimated glomerular filtration rate (eGFR), (2) whether the significantly associated markers are also associated with traditional risk factors and/or novel biomarkers for eGFR, and (3) how much additional variation in eGFR is explained by epigenetic markers beyond established risk factors and biomarkers. The majority of methylation markers most significantly associated with eGFR (24 out of the top 30) appeared to function, at least in part, through pathways related to aging, inflammation, or cholesterol. However, six epigenetic markers were still able to significantly predict eGFR after adjustment for other risk factors. This work shows that epigenetic markers may offer valuable new insight into the complex pathophysiology of CKD in African Americans. 1. Introduction Chronic kidney disease (CKD) is an increasing public health concern in the United States due to its rapidly rising incidence and prevalence, particularly among older individuals. While about 20 million United States adults over the age of 20 (10%) currently have CKD, the prevalence of CKD among those 60 and older is approximately 25% [1]. Further, the incidence of CKD among those aged 65 and older more than doubled between 2000 and 2008 [1]. As a result, health care costs related to the most severe form of CKD, End-Stage Renal Disease (ESRD), have also nearly doubled in the past decade to over $40 billion per year [1]. Individuals over 60 are almost 6 times more likely to develop CKD than those aged 20–39, and females are 1.4 times more likely than males to develop it [2]. Further, African Americans are at higher risk for ESRD than other races. While African Americans accounted for only 12% of the US population in 2009, they accounted for nearly one-third of kidney failure cases [3]. Level of kidney function is assessed by the glomerular filtration rate (GFR), the rate at which blood passes through the kidney’s filtering mechanisms. GFR levels below 60？mL/min/1.732？m2 are used, in conjunction with markers of kidney damage such as proteinuria, to diagnose CKD
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