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Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR
Nature Communications ( IF 16.6 ) Pub Date : 2020-11-24 , DOI: 10.1038/s41467-020-19615-x
Alicia K Smith 1, 2 , Andrew Ratanatharathorn 3 , Adam X Maihofer 4 , Robert K Naviaux 5 , Allison E Aiello 6 , Ananda B Amstadter 7 , Allison E Ashley-Koch 8 , Dewleen G Baker 4, 9, 10 , Jean C Beckham 11, 12, 13 , Marco P Boks 14 , Evelyn Bromet 15 , Michelle Dennis 11, 13 , Sandro Galea 16 , Melanie E Garrett 8 , Elbert Geuze 14, 17 , Guia Guffanti 18, 19 , Michael A Hauser 8, 20 , Seyma Katrinli 1 , Varun Kilaru 1 , Ronald C Kessler 19 , Nathan A Kimbrel 11, 12, 13 , Karestan C Koenen 21, 22, 23 , Pei-Fen Kuan 24 , Kefeng Li 25 , Mark W Logue 26, 27, 28, 29 , Adriana Lori 2 , Benjamin J Luft 30 , Mark W Miller 26, 27 , Jane C Naviaux 31 , Nicole R Nugent 32 , Xuejun Qin 8 , Kerry J Ressler 2, 18, 19 , Victoria B Risbrough 4, 9, 10 , Bart P F Rutten 33 , Murray B Stein 4, 9, 34 , Robert J Ursano 35 , Eric Vermetten 14, 35, 36, 37, 38 , Christiaan H Vinkers 39, 40 , Lin Wang 25 , Nagy A Youssef 41 , , , , Monica Uddin 42 , Caroline M Nievergelt 4, 9, 10
Affiliation  

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.



中文翻译:

跨 10 个军事和平民队列的 PTSD 的表观基因组范围的荟萃分析确定了 AHRR 的甲基化变化

表观遗传差异可能有助于区分 PTSD 病例和创伤暴露对照。在这里,我们描述了迄今为止最大的 PTSD DNA 甲基化荟萃分析的结果。十个队列,军事和平民,提供来自 1,896 PTSD 病例和创伤暴露对照的血液来源的 DNA 甲基化数据。在对多重比较进行调整后,芳基烃受体阻遏物 ( AHRR)内的四个 CpG 位点与 PTSD 相关,与对照相比,PTSD 病例中的 DNA 甲基化较低。尽管已知AHRR甲基化与吸烟有关,但AHRR与 PTSD 的关联在非吸烟者中最为明显,表明该结果与吸烟状况无关。代谢组学数据的评估表明AHRR与犬尿氨酸水平相关的甲基化,在患有 PTSD 的受试者中较低。该研究支持 PTSD 患者的表观遗传差异,并表明犬尿氨酸减少是 PTSD 免疫失调的一个促成因素。

更新日期:2020-11-25
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