Severity of Idiopathic Scoliosis Is Associated with Differential Methylation: An Epigenome-Wide Association Study of Monozygotic Twins with Idiopathic Scoliosis.
Severity of Idiopathic Scoliosis Is Associated with Differential Methylation: An Epigenome-Wide Association Study of Monozygotic Twins with Idiopathic Scoliosis.
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特发性脊柱侧凸的严重程度与差异甲基化相关：一项对特发性脊柱侧凸同卵双胞胎的表观基因组关联研究。
DOI：
10.3390/genes12081191
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发表时间：
2021-07-30
期刊：
影响因子：
3.5
通讯作者：
Hadley-Miller N
中科院分区：
文献类型：
--
作者：
Carry PM;Terhune EA;Trahan GD;Vanderlinden LA;Wethey CI;Ebrahimi P;McGuigan F;Åkesson K;Hadley-Miller N
表观遗传机制可能导致特发性脊柱侧凸（IS）。我们确定了8对同卵双生子IS，6个不一致（Cobb角差> 10°）和2个一致（Cobb角差≤ 2°）。使用Infinium HumanMethylation EPIC Beadchip测量血液中的全基因组甲基化。我们测试了不一致双胞胎之间甲基化和甲基化变异性的差异，并测试了所有双胞胎中甲基化和曲线严重程度之间的相关性。差异甲基化区域（DMR）分析鉴定了基因启动子区域。在cg 12959265（chr. 7 DPY 19 L1）处的甲基化在病例中变化较小（错误发现率（FDR）= 0.0791）。我们鉴定了四种探针（错误发现率，FDR < 0.10）; cg 02477677（chr. 17，RARA基因）、cg 12922161（chr. 2 LOC 150622基因）、cg 08826461（chr. 2）和cg 16382077（chr. 7）与曲线严重性相关。我们确定了57个DMR，其中高甲基化或低甲基化在整个地区是一致的，28个DMR与曲线严重程度一致相关。在DMR中，21例与骨甲基化相关。基于骨中甲基化一致性的区域优先化鉴定了WNT 10A（WNT信号传导）、NPY（骨和能量稳态的调节剂）和预测与骨形成/重塑相关的其他启动子区域。这些区域可能有助于理解遗传、环境和IS之间复杂的相互作用。
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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影响因子：
2
作者：
Marosy, Beth;Justice, Cristina M.;Vu, Cuong;Zorn, Andrew;Nzegwu, Nneka;Wilson, Alexander F.;Miller, Nancy H.
通讯作者：
Miller, Nancy H.
影响因子：
3.7
作者：
Einarsdottir E;Grauers A;Wang J;Jiao H;Escher SA;Danielsson A;Simony A;Andersen M;Christensen SB;Åkesson K;Kou I;Khanshour AM;Ohlin A;Wise C;Ikegawa S;Kere J;Gerdhem P
通讯作者：
Gerdhem P
影响因子：
4.1
作者：
Cawthorn WP;Bree AJ;Yao Y;Du B;Hemati N;Martinez-Santibañez G;MacDougald OA
通讯作者：
MacDougald OA
影响因子：
4.4
作者：
Evans, HK;Wylie, AA;Jirtle, RL
通讯作者：
Jirtle, RL
DOI：
10.1534/g3.114.015669
发表时间：
2014-12-12
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Baschal EE;Wethey CI;Swindle K;Baschal RM;Gowan K;Tang NL;Alvarado DM;Haller GE;Dobbs MB;Taylor MR;Gurnett CA;Jones KL;Miller NH
通讯作者：
Miller NH