Common epigenetic variation in a European population of mentally healthy young adults

Abstract

DNA methylation represents an important link between structural genetic variation and complex phenotypes. The study of genome-wide CpG methylation and its relation to traits relevant to psychiatry has become increasingly important. Here, we analyzed quality metrics of 394,043 CpG sites in two samples of 568 and 319 mentally healthy young adults. For 25% of all CpGs we observed medium to large common epigenetic variation. These CpGs were overrepresented in open sea and shore regions, as well as in intergenic regions. They also showed a strong enrichment of significant hits in association analyses. Furthermore, a significant proportion of common DNA methylation is at least partially genetically driven and thus may be observed similarly across tissues. These findings could be of particular relevance for studies of complex neuropsychiatric traits, which often rely on proxy tissues.

Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts

“…Further, we found a significant association of CpG site cg17519949 with SNP rs2074621, indicating SNP rs2074621 as a meQTL, likely to affect the methylation level of this CpG site. This assumption is further supported by the results of Milnik et al (), who found enrichment of meQTLs among CpGs with medium to large epigenetic variability, as was the case with cg17519949 that is located within an exon (Human GRCh37/hg19; Kent et al, ) and thus could be involved in the regulation of gene expression. It is now widely accepted that NOTCH transcription and translation is negatively regulated by microRNAs, which consequently affects the intensity of NOTCH signaling (Dias et al, ).…”

Exhaustive search for epistatic effects on the human methylome

“…We used data from two independent samples of healthy young adults from the general population (discovery sample N = 533, replication sample N = 319; see Table 1 ; DNA was derived from blood, see Methods) 25 . With these sample-sizes we were adequately powered to detect and replicate medium to strong effect sizes in an exhaustive search (see Fig.…”

“…We performed an additional search for interaction effects, based on SNPs in proximity to the CpG (defined as 3.5 MB window, number of SNPs per CpG ranging from 1 to 3,290, mean = 1,223) that show a significant main effect. The 3.5 MB window comprises >95% of all main effects from SNPs on CpGs 25 . By focusing on SNPs being located in proximity to CpGs and exhibiting main effects, this approach was computationally less expensive ( N = 4.84 × 10 8 main effects and N = 7,173,795 interaction effects tested) in comparison to the exhaustive search ( N = 7.36 × 10 15 interaction analyses).…”

“…The PCA was based on CpGs with no missing values ( >95% of the included CpGs). The PCA-based approach corrected for technical biases as well as for part of the variability induced by blood cell composition 25 (4) regressing out the effects of sex and age; (5) regressing out the effects of variants in the 50mer probe sequence, if the total variance explained by these variants exceeded 0.1% (see below). The accepted missing rate per CpG was set to <1% in both samples.…”

8th Santorini Conference: Systems medicine and personalized health and therapy, Santorini, Greece, 3–5 October 2016

“…He introduced us into the wide field of epigenetic modifications and more specifically, into the DNA methylation undergoing with age [6]. Methylation regulates imprinting, chromosomal inactivation and gene expression.…”