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Evidence suggests that the risk variants, which show a recessive mode of inheritance, lead to toxic gain-of-function changes of the APOL1 protein. Disease occurrence and presentation vary, likely due to modifiers or second hits. To understand the role of the epigenetic landscape in relation to <jats:italic>APOL1<\/jats:italic> risk variants, we performed methylation quantitative trait locus (meQTL)\u00a0analysis to identify differentially methylated CpGs influenced by <jats:italic>APOL1<\/jats:italic>\u00a0risk variants in 611 African American individuals. We identified five CpGs\u00a0that were significantly associated with <jats:italic>APOL1<\/jats:italic> risk alleles in discovery and replication studies, and one CpG-<jats:italic>APOL1<\/jats:italic> association was independent of other genomic variants. Our study highlights proximal DNA methylation alterations  that may help explain the variable disease risk and clinical manifestation of <jats:italic>APOL1<\/jats:italic> variants.<\/jats:p>","DOI":"10.1186\/s12864-024-10226-0","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T03:37:18Z","timestamp":1715139438000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["African ancestry-derived APOL1 risk genotypes show proximal epigenetic associations"],"prefix":"10.1186","volume":"25","author":[{"given":"Charles E.","family":"Breeze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget M.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl A.","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Franceschini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"10226_CR1","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1126\/science.1193032","volume":"329","author":"G Genovese","year":"2010","unstructured":"Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, et al. 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The research conforms to the principles of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"452"}}