| Autor: |
Carry PM; Musculoskeletal Research Center, Children's Hospital Colorado, Aurora, CO 80045, USA.; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Terhune EA; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Trahan GD; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Vanderlinden LA; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA., Wethey CI; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Ebrahimi P; Clinical Sciences Malmo, Clinical and Molecular Osteoporosis Research Unit, Lund University, S-205 02 Malmö, Sweden., McGuigan F; Clinical Sciences Malmo, Clinical and Molecular Osteoporosis Research Unit, Lund University, S-205 02 Malmö, Sweden., Åkesson K; Clinical Sciences Malmo, Clinical and Molecular Osteoporosis Research Unit, Lund University, S-205 02 Malmö, Sweden.; Department of Orthopedics, Skane University Hospital, S-205 02 Malmö, Sweden., Hadley-Miller N; Musculoskeletal Research Center, Children's Hospital Colorado, Aurora, CO 80045, USA.; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. |
| Abstrakt: |
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. |
