| 1. |
|
|
| 2. |
|
|
| 3. |
- Carry, Patrick M., et al.
(author)
-
Severity of idiopathic scoliosis is associated with differential methylation : An epigenome‐wide association study of monozygotic twins with idiopathic scoliosis
- 2021
-
In: Genes. - : MDPI AG. - 2073-4425. ; 12:8
-
Journal article (peer-reviewed)abstract
- Epigenetic mechanisms may contribute to idiopathic scoliosis (IS). We identified 8 monozygotic twin pairs with IS, 6 discordant (Cobb angle difference >10°) and 2 concordant (Cobb angle difference ≤2°). Genome‐wide methylation in blood was measured with the Infinium HumanMethylation EPIC Beadchip. We tested for differences in methylation and methylation variability between discordant twins and tested the association between methylation and curve severity in all twins. Differentially methylated region (DMR) analyses identified gene promoter regions. Methylation at cg12959265 (chr. 7 DPY19L1) was less variable in cases (false discovery rate (FDR) = 0.0791). We identified four probes (false discovery rate, FDR < 0.10); cg02477677 (chr. 17, RARA gene), cg12922161 (chr. 2 LOC150622 gene), cg08826461 (chr. 2), and cg16382077 (chr. 7) associated with curve severity. We identified 57 DMRs where hyper‐ or hypo‐methylation was consistent across the region and 28 DMRs with a consistent association with curve severity. Among DMRs, 21 were correlated with bone methylation. Prioritization of regions based on methylation concordance in bone identified promoter regions for WNT10A (WNT signaling), NPY (regulator of bone and energy homeostasis), and others predicted to be relevant for bone formation/remodeling. These regions may aid in understanding the complex interplay between genetics, environment, and IS.
|
|
| 4. |
- Ebrahimi, Parvaneh, et al.
(author)
-
Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation–can blood be used as a surrogate for bone?
- 2021
-
In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 16:1, s. 92-105
-
Journal article (peer-reviewed)abstract
- Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene–environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecular bone and peripheral blood collected from the same patients at the same time-point (n = 12 women; 66–85y), to investigate the between-tissue correspondence. What constituted a CpG site with corresponding methylation in both tissues was stringently defined. Only sites highly correlated (r2 > 0.74; FDR q-value <0.05) and at least 80% similarity in methylation level (Δβ <0.2) between paired samples were retained. In total, 28,549 CpG sites were similarly methylated in bone and blood. Between 33% and 49% of loci associated with bone phenotypes through GWAS were represented among these sites, and major pathways relevant to bone regulation were enriched. The results from this study indicate that blood can mirror the bone methylome and capture sites related to bone regulation. This study shows that in principal, peripheral blood is a feasible surrogate for bone tissue in DNA methylation investigations. As the first step, this will provide a platform for future studies in bone epigenetics, and possibly for larger-scale epidemiological studies.
|
|
| 5. |
|
|
