SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans.
SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans.
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DOI：
10.1038/mp.2015.134
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发表时间：
2016-03
影响因子：
11
通讯作者：
Miller MW
中科院分区：
文献类型：
--
作者：
Sadeh N;Spielberg JM;Logue MW;Wolf EJ;Smith AK;Lusk J;Hayes JP;Sperbeck E;Milberg WP;McGlinchey RE;Salat DH;Carter WC;Stone A;Schichman SA;Humphries DE;Miller MW
最近，SKA2基因甲基化已被确定为一个有希望的自杀风险的生物标志物。基于这一发现，我们研究了SKA2甲基化、皮质厚度和精神表型与创伤暴露退伍军人自杀的关系。在最近的伊拉克和阿富汗冲突中，200名暴露在创伤中的非西班牙裔白人退伍军人(91%为男性)接受了临床评估，并抽血进行了基因分型和甲基化分析。145名参与者也有可用的神经成像数据。基于先前的研究，我们检测了CpG基因座cg13989295的DNA甲基化以及甲基化相关SNP(Rs7208505)上的DNA甲基化调整与全脑皮质厚度、创伤后应激障碍症状(PTSD)和抑郁症状的关系。全脑顶点分析确定了前额叶皮质中与基因调整后的SKA2 DNA甲基化(甲基化调整)相关的三个簇。具体地说，DNA甲基化adj与双侧额叶极部和额上回皮质厚度的减少有关，在右侧眶前皮质和右额下回也发现了类似的影响。PTSD症状严重程度与SKA2、DNA甲基化水平呈正相关，与皮质厚度呈负相关。中介分析显示创伤后应激障碍通过SKA2甲基化状态对皮质厚度有显著的间接影响。结果表明，血液指标中SKA2的DNA甲基化调整与应激相关的精神表型和神经生物学有关，表明其作为应激暴露和易感性的生物标志物的潜在价值。
Methylation of the SKA2 gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness, and psychiatric phenotypes linked to suicide in trauma-exposed veterans. 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the CpG locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated SNP (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD), and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylationadj). Specifically, DNA methylationadj was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylationadj and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylationadj of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility.