Meta-analyses identify DNA methylation associated with kidney function and damage.
Pascal SchlosserAdrienne TinPamela R Matias-GarciaChris H L ThioRoby JoehanesHongbo LiuAntoine WeihsZhi YuAnselm HoppmannFranziska Grundner-CulemannJosine L MinAdebowale A AdeyemoCharles AgyemangJohan ÄrnlövNasir Ahmad AzizAndrea A BaccarelliMurielle BochudHermann BrennerMonique M B BretelerCristian CarmeliLayal ChakerJohn C ChambersShelley A ColeJosef CoreshTanguy CorreAdolfo CorreaSimon R CoxNiek de KleinGraciela E DelgadoArce Domingo-RellosoKai Uwe EckardtArif Bülent EkiciKarlhans EndlichKathryn L EvansJames S FloydMyriam FornageLude FrankeEliza FraszczykXu GaoXin GàoMohsen GhanbariSahar GhasemiChristian GiegerPhilip GreenlandMegan L GroveSarah E HarrisGibran HemaniPeter HennemanChristian HerderSteve HorvathLifang HouMarjo-Riitta JarvelinShih-Jen HwangMarjo-Riitta JarvelinSharon L R KardiaSilva KaselaMarcus Edi KleberWolfgang KoenigJaspal S KoonerHolly KramerFlorian KronenbergBrigitte KühnelTerho LehtimäkiLars LindDan LiuYongmei LiuDonald M Lloyd-JonesKurt LohmanStefan LorkowskiAke T LuRiccardo E MarioniWinfried MärzDaniel L McCartneyKarlijn Anna Catharina MeeksLili A MilaniPashupati P MishraMatthias NauckAna Navas-AcienChristoph NowakAnnette PetersHolger ProkischBruce M PsatyOlli T RaitakariScott M RatliffAlexander P ReinerSylvia E RosasBen SchöttkerJoel SchwartzSanaz SedaghatJennifer A SmithNona SotoodehniaHannah R StockerSilvia StringhiniJohan SundströmBrenton R SwensonMaria Tellez-PlazaJoyce B J van MeursJana V Van Vliet-OstaptchoukAndrea VenemaNiek VerweijRosie M WalkerMatthias WielscherJuliane WinkelmannBruce H R WolffenbuttelWei ZhaoYinan Zhengnull nullnull nullMarie LohHarold SniederDaniel LevyMelanie WaldenbergerKatalin SusztákAnna KottgenAlexander TeumerPublished in: Nature communications (2021)
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.