Self-Reported Race as a Determinant of Differential Methylation in Peripheral Artery Disease

Peripheral Artery Disease (PAD) is a manifestation of atherosclerosis within the lower extremities that affects approximately 10 million people in the United States. Despite the rising prevalence of PAD, Black Americans are disproportionately affected and experience worse outcomes, including higher rates of limb loss compared to White counterparts. To dissect mechanisms within PAD, we performed DNA methylation analysis utilizing methyl-binding domain-capture sequencing. Within the DNA methylation profiles, we observe a large driver of variation is self-reported race. Specifically, samples separate into White and Black groups. Interestingly, when comparing PAD to Control samples within each self-reported racial group, there are different differentially methylated CpGs between the two groups. This suggests that the methylation landscape both at baseline and in disease is different based on self-reported racial background and could begin to explain some of the differences we see in downstream outcomes between White and Black Americans. Overall design: prospective cohort