Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure

Abstract

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P <1×10 −5 . In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated ( P <1×10 −7 ) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P <0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 ( TXNIP ) and cg00716257 ( JDP2 ) determined by environmental effects acting on both systolic BP and methylation levels.

Unique Associations of DNA Methylation Regions With 24-Hour Blood Pressure Phenotypes in Black Participants

“…Although our study failed to show significant associations of clinic BPs with specific MRs after correction for FDR <0.05, previous studies have reported associations of DNA methylation at several genomic loci in whole blood with clinic BP levels in thousands of subjects. 7,11,34 Several of these CpG sites were associated with various BP phenotypes in our study with marginal significance, demonstrating consistency with prior studies. However, despite the strengths of our methods of MR analysis, the sample size may have limited the statistical power for identifying significant associations between DNA methylation and clinic BP in the current study.…”

Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

“…Pre-eclampsia is strongly associated with later-life blood pressure, and (oddly) inversely associated with smoking [ 37 ]. We examined previous analyses of DNA methylation for high blood pressure [ 38 ] and smoking [ 39 ] in this cohort, and did not identify any overlapping differentially methylated sites (Additional file 1 : Table S4).…”

Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

“…All three twin cohorts have been studied in an intensive longitudinal manner, and several subprojects have been conducted in laboratory conditions. All twins who had taken part in clinical in-person sub-studies with sampling for both whole blood and muscle tissue, subsequent DNA methylation analyses and phenotype collection were included ( N = 139) [ 39 , 40 ]. The dataset comprises two age groups: young adults from 23 to 44 years of age ( N = 93) and older adults from 57 to 69 years of age ( N = 46).…”