biostudies-literatureMa YNIA NIH HHSMedical Research CouncilRosetreesNational Institute on AgingParkinson's UKe12964https://www.ebi.ac.uk/biostudies/studies/S-EPMC6612647biostudies-literatureUnknown18(4)CpG-related single nucleotide polymorphisms (CGS) have the potential to perturb DNA methylation; however, their effects on Alzheimer disease (AD) risk have not been evaluated systematically. We conducted a genome-wide association study using a sliding-window approach to measure the combined effects of CGSes on AD risk in a discovery sample of 24 European ancestry cohorts (12,181 cases, 12,601 controls) from the Alzheimer's Disease Genetics Consortium (ADGC) and replication sample of seven European ancestry cohorts (7,554 cases, 27,382 controls) from the International Genomics of Alzheimer's Project (IGAP). The potential functional relevance of significant associations was evaluated by analysis of methylation and expression levels in brain tissue of the Religious Orders Study and the Rush MAging cellCpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease.PMC6612647U24-AG041689-01P30 AG053760P50 AG0051461494371P50 AG005142MR/L501517/1P50 AG047266MR/N026004/1P30 AG019610R01 AG0489271498735RC2AG036528P50 AG008702P30 AG010124P30 AG012300P50 AG047270MR/L501542/1P30 AG010161G0701075G-0907R01-AG048927UKDRI-1009R01 AG036042R01-AG36042P30 AG049638U01 AG032984U24 AG041689G0902227G0901254R01 AG015819P30 AG013846P30 AG028383P30 AG008017P30 AG010133P50 AG033514RF1 AG036042R01-AG17917MR/K01417X/1M733P50 AG005681U01-AG032984P50 AG047366P30-AG10161U24 AG021886G0300429RF1 AG054023P50 AG023501P30 AG008051U01-AG46152MR/K013041/1MR/M009076/1P30 AG010129P30 AG013854P50 AG005138P50 AG005134U01 AG016976P50 AG005136P50 AG025688P30 AG035982P50 AG005131P50 AG005133RC2 AG036528MR/L023784/2MR/L023784/1P50 AG016574RF1 AG057519U24 AG056270RF1-AG057519P50 AG016573R01 AG017917Jun GRMayeux RMa YNaj ACSchellenberg GDLunetta KLChung JHaines JLKunkle BWPericak-Vance MABennett DAZhang XFarrer LAAlzheimer’s Disease Genetics ConsortiumWhite CCDe Jager PLfalseCpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease.CpG-related single nucleotide polymorphisms (CGS) have the potential to perturb DNA methylation; however, their effects on Alzheimer disease (AD) risk have not been evaluated systematically. We conducted a genome-wide association study using a sliding-window approach to measure the combined effects of CGSes on AD risk in a discovery sample of 24 European ancestry cohorts (12,181 cases, 12,601 controls) from the Alzheimer's Disease Genetics Consortium (ADGC) and replication sample of seven European ancestry cohorts (7,554 cases, 27,382 controls) from the International Genomics of Alzheimer's Project (IGAP). The potential functional relevance of significant associations was evaluated by analysis of methylation and expression levels in brain tissue of the Religious Orders Study and the Rush M2019-01-01T00:00:00Z2019 Aug2026-05-07T06:53:52.147Z2019-08-07T07:04:08ZS-EPMC66126473114444310.1111/acel.12964