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Severity of idiopathic scoliosis is associated with differential methylation : An epigenome‐wide association study of monozygotic twins with idiopathic scoliosis

Carry, Patrick M. ; Terhune, Elizabeth A. ; Trahan, George D. ; Vanderlinden, Lauren A. ; Wethey, Cambria I. ; Ebrahimi, Parvaneh LU ; McGuigan, Fiona LU orcid ; Åkesson, Kristina LU and Hadley‐Miller, Nancy (2021) In Genes 12(8).
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bone, Curve severity, Differentially methylated region, Discordant, DNA methylation, Epigenome‐wide association study, Idiopathic scoliosis, Monozygotic twin
in
Genes
volume
12
issue
8
article number
1191
publisher
MDPI AG
external identifiers
  • scopus:85112631480
  • pmid:34440365
ISSN
2073-4425
DOI
10.3390/genes12081191
language
English
LU publication?
yes
id
777dc443-bd17-4a52-bc1e-f20ab624be8a
date added to LUP
2021-09-23 10:05:19
date last changed
2024-04-20 11:46:05
@article{777dc443-bd17-4a52-bc1e-f20ab624be8a,
  abstract     = {{<p>Epigenetic mechanisms may contribute to idiopathic scoliosis (IS). We identified 8 monozygotic twin pairs with IS, 6 discordant (Cobb angle difference &gt;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 &lt; 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.</p>}},
  author       = {{Carry, Patrick M. and Terhune, Elizabeth A. and Trahan, George D. and Vanderlinden, Lauren A. and Wethey, Cambria I. and Ebrahimi, Parvaneh and McGuigan, Fiona and Åkesson, Kristina and Hadley‐Miller, Nancy}},
  issn         = {{2073-4425}},
  keywords     = {{Bone; Curve severity; Differentially methylated region; Discordant; DNA methylation; Epigenome‐wide association study; Idiopathic scoliosis; Monozygotic twin}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{MDPI AG}},
  series       = {{Genes}},
  title        = {{Severity of idiopathic scoliosis is associated with differential methylation : An epigenome‐wide association study of monozygotic twins with idiopathic scoliosis}},
  url          = {{http://dx.doi.org/10.3390/genes12081191}},
  doi          = {{10.3390/genes12081191}},
  volume       = {{12}},
  year         = {{2021}},
}