Abstract:
BACKGROUND:Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-analysis. RESULTS:Stage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 × 10-08) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region. CONCLUSIONS:This study suggests that the development of combat-related PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent findings suggest the involvement of the immune system through the HLA region and HEXDC, and MAD1L1 which was previously associated with PTSD.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Snijders C,Maihofer AX,Ratanatharathorn A,Baker DG,Boks MP,Geuze E,Jain S,Kessler RC,Pishva E,Risbrough VB,Stein MB,Ursano RJ,Vermetten E,Vinkers CH,PGC PTSD EWAS Consortium.,Smith AK,Uddin M,Rutten BPF,Nievergelt CMdoi
10.1186/s13148-019-0798-7subject
Has Abstractpub_date
2020-01-13 00:00:00pages
11issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-019-0798-7journal_volume
12pub_type
杂志文章abstract::[This corrects the article DOI: 10.1186/s13148-016-0190-9.]. ...
journal_title:Clinical epigenetics
pub_type: 已发布勘误
doi:10.1186/s13148-016-0250-1
更新日期:2016-08-04 00:00:00
abstract:BACKGROUND:Kawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication. Typically, DNA methylation is thought to repress the expression of nearby genes. However, the cases in which DNA methylation promotes gene expression have been reported. In additi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0557-1
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Preeclampsia, a pregnancy complication of placental origin is associated with altered expression of angiogenic factors and their receptors. Recently, there is considerable interest in understanding the role of adverse intrauterine conditions in placental dysfunction and adverse pregnancy outcomes. Since we h...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-6
更新日期:2013-04-26 00:00:00
abstract:BACKGROUND:The pathogenesis of systemic lupus erythematosus (SLE) has not yet been completely elucidated. One of the hallmarks of SLE is the production of autoantibodies by uncontrolled over-activated B cells. Early B cell factor 1 (EBF1) contributes to the development, activation, and proliferation of B cells through ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0063-7
更新日期:2015-03-14 00:00:00
abstract:BACKGROUND:Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neopla...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0559-z
更新日期:2018-10-19 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a multisystemic disorder that affects 1:5000 boys. The severity of the phenotype varies dependent on the mutation site in the DMD gene and the resultant dystrophin expression profile. In skeletal muscle, dystrophin loss is associated with the disintegration of myofibers and their i...
journal_title:Clinical epigenetics
pub_type: 杂志文章,评审
doi:10.1186/s13148-021-01001-z
更新日期:2021-01-19 00:00:00
abstract:BACKGROUND:Epigenetic changes in DNA methylation could regulate the expression of several allergy-related genes. We investigated whether tolerance acquisition in children with immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is characterized by a specific DNA methylation profile of Th2 (IL-4, IL-5) and Th1 (IL-...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0070-8
更新日期:2015-03-31 00:00:00
abstract::Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smok...
journal_title:Clinical epigenetics
pub_type: 杂志文章,评审
doi:10.1186/s13148-016-0210-9
更新日期:2016-04-22 00:00:00
abstract:BACKGROUND:Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0054-8
更新日期:2015-02-27 00:00:00
abstract:BACKGROUND:Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal prog...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-0824-9
更新日期:2020-02-19 00:00:00
abstract:BACKGROUND:The transcription factor Snail2 is a repressor of E-cadherin expression during carcinogenesis; however, the specific mechanisms involved in this process in human colorectal cancer (CRC) remain largely unknown. METHOD:We checked the expression of Snail2 in several clinical CRC specimens. Then, we established...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0592-y
更新日期:2018-12-12 00:00:00
abstract:BACKGROUND:Normal-weight polycystic ovary syndrome (PCOS) women exhibit adipose resistance in vivo accompanied by enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with accelerated lipid accumulation per cell in vitro. The present study examines chromatin accessibility, RNA expressi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00970-x
更新日期:2020-11-23 00:00:00
abstract:BACKGROUND:The mechanism of action of olanzapine in treating schizophrenia is not clear. This research reports the effects of a therapeutic equivalent treatment of olanzapine on DNA methylation in a rat model in vivo.Genome-wide DNA methylation was assessed using a MeDIP-chip analysis. All methylated DNA immunoprecipit...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-6-1
更新日期:2014-01-02 00:00:00
abstract:BACKGROUND:About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We theref...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0161-6
更新日期:2015-12-12 00:00:00
abstract:BACKGROUND:Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which bec...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0377-8
更新日期:2017-08-14 00:00:00
abstract:BACKGROUND:DNA methylation is a well-studied epigenetic mark that is frequently altered in diseases such as cancer, where specific changes are known to reflect the type and severity of the disease. Therefore, there is a growing interest in assessing the clinical utility of DNA methylation as a biomarker for diagnosing ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00880-y
更新日期:2020-06-22 00:00:00
abstract::Heterozygous mutation of the transcription factor HNF1B is the most common cause of monogenetic developmental renal disease. Disease-associated mutations fall into two categories: HNF1B intragenic mutations and a 1.3 Mb deletion at chromosome 17q12. An increase in neurodevelopmental disorders has been observed in indi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0530-z
更新日期:2018-07-18 00:00:00
abstract:Background:This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods:A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0432-5
更新日期:2017-12-20 00:00:00
abstract:BACKGROUND:The introduction of pathology tissue-chromatin immunoprecipitation (PAT-ChIP), a technique allowing chromatin immunoprecipitation (ChIP) from formalin-fixed paraffin-embedded (FFPE) tissues, has extended the application of chromatin studies to clinical patient samples. However, extensive crosslinking introdu...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0576-y
更新日期:2018-11-16 00:00:00
abstract:BACKGROUND:Activation of transcription enhancers, especially super-enhancers, is one of the critical epigenetic features of tumorigenesis. However, very few studies have systematically identified the enhancers specific in cancer tissues. METHODS:Here, we studied the change of histone modifications in MMTV-PyVT breast ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0645-x
更新日期:2019-03-12 00:00:00
abstract:INTRODUCTION:DNA methylation of CpG islands within the promoter region of genes is an epigenetic modification with an important role in the development of cancer and it is typically mediated by DNA methyltransferases (DNMTs). In cancer cells, global hypomethylation of the genome as a whole and regional hypermethylation...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-7
更新日期:2013-05-02 00:00:00
abstract:BACKGROUND:Epigenetic mechanisms may partly explain the persistent effects of adverse childhood experiences (ACEs) on health outcomes in later life. DNA methylation can predict chronological age, and advanced methylation-predicted age beyond chronological age (DNA methylation age acceleration) is associated with ACEs, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00844-2
更新日期:2020-04-07 00:00:00
abstract:BACKGROUND:The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race a...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0080-6
更新日期:2015-04-21 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0152-7
更新日期:2015-11-05 00:00:00
abstract:BACKGROUND:Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular disease (CVD) by 44% and in diabetic CVD patients by 57% on top of statins. A phase III trial, BETonM...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0696-z
更新日期:2019-07-12 00:00:00
abstract:BACKGROUNDS:Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizz...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00
abstract:BACKGROUND:ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It is caused by truncating mutations in ADNP, which is involved in chromatin regulation. We hypothesized that the disruption of chromatin regulation might result in specific DNA methyl...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0658-5
更新日期:2019-04-27 00:00:00
abstract:BACKGROUND:The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigen...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0177-6
更新日期:2016-01-28 00:00:00
abstract:Background:Maternal social environmental stressors during pregnancy are associated with adverse birth and child developmental outcomes, and epigenetics has been proposed as a possible mechanism for such relationships. Methods:In a Mexican-American birth cohort of 241 maternal-infant pairs, cord blood samples were meas...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0494-z
更新日期:2018-05-08 00:00:00
abstract:BACKGROUND:B vitamins in the one-carbon metabolism pathway (folate, vitamin B6, and vitamin B12) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-019-0741-y
更新日期:2019-10-11 00:00:00