biostudies-literatureMa JNHLBI NIH HHSNIAAA NIH HHS19564https://www.ebi.ac.uk/biostudies/studies/S-EPMC9664436biostudies-literatureUnknown12(1)DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trait loci (mQTLs) in 4126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) at P < 1e-7 and 33,572,145 trans-mQTL variant-CpG pairs (for 213,606 unique autosomal CpGs) at P < 1e-14. Using cis-mQTL variants for 1258 CpGs associated with seven cardiovascular disease (CVD) risk factors, we found 104 unique CpGs that colocalized with at least one CVD trait. For example, cg11554650 (PPP1R18) colocalized with type 2 diabetes, and was driven by a single nucleotide polymorphism (rs2516396). We performed MendeScientific reportsElucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease.PMC9664436U01 HL120393R01 HL12039375N92019D00031HHSN268201000021CK22 HL135075R01 HL155569HHSN268201500001IN01HC25195HHSN268201000001IR01 AA028263Heard-Costa NLVasan RSBui HSooda MCourchesne PKeshawarz APitsillides ANHwang SJSharopova NHuan TMunson PJLevy DTejada BMa JDemirkale CYLiu CJoehanes RFeolo MfalseElucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease.DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trait loci (mQTLs) in 4126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) at P < 1e-7 and 33,572,145 trans-mQTL variant-CpG pairs (for 213,606 unique autosomal CpGs) at P < 1e-14. Using cis-mQTL variants for 1258 CpGs associated with seven cardiovascular disease (CVD) risk factors, we found 104 unique CpGs that colocalized with at least one CVD trait. For example, cg11554650 (PPP1R18) colocalized with type 2 diabetes, and was driven by a single nucleotide polymorphism (rs2516396). We performed Mende2022-01-01T00:00:00Z2022 Nov2026-04-08T18:20:36.333Z2025-02-19T01:28:39.898ZS-EPMC96644363638012110.1038/s41598-022-24100-0