Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts.

Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues.

No association of posttraumatic stress disorder with epigenetic aging in women at mid-life: A longitudinal cohort study.

Posttraumatic stress disorder (PTSD) is associated with mortality and increased risk of diseases of aging, but underlying mechanisms remain unclear. We examine associations of PTSD with one potential pathway, accelerated epigenetic aging. In a longitudinal cohort of trauma-exposed middle-aged women (n = 831, n observations = 1,516), we examined cross-sectional and longitudinal associations between PTSD, with and without comorbid depression, and epigenetic aging measured by six clocks at two time points approximately 13.

Cross omics risk scores of inflammation markers are associated with all-cause mortality: The Canadian Longitudinal Study on Aging.

Inflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (Polygenic-Risk-Score; PRS), metabolomics (Metabolomic-Risk-Score; MRS), and epigenetics (Epigenetic-Risk-Score; ERS) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFa).

Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers.

Childhood maltreatment and health in the UK Biobank: triangulation of outcome-wide and polygenic risk score analyses.

Background: Childhood maltreatment is common globally and impacts morbidity, mortality, and well-being. Our understanding of its impact is constrained by key substantive and methodological limitations of extant research, including understudied physical health outcomes and bias due to unmeasured confounding. We address these limitations through a large-scale outcome-wide triangulation study.

Polygenic risk for major depression, attention deficit hyperactivity disorder, neuroticism, and schizophrenia are correlated with experience of intimate partner violence.

Research has suggested that mental illness may be a risk factor for, as well as a sequela of, experiencing intimate partner violence (IPV). The association between IPV and mental illness may also be due in part to gene-environment correlations. Using polygenic risk scores for six psychiatric disorders - attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), neuroticism, and schizophrenia-and a combined measure of overall genetic risk for mental illness, we tested whether women's genetic risk for mental illness was associated with the experience of three types of intimate partner violence.

A flexible matching strategy for matched nested case-control studies.

Purpose: Individual matching in case-control studies improves statistical efficiency over random selection of controls but can lead to selection bias if cases are excluded due to the lack of appropriate controls or residual confounding with less strict matching criteria. We introduce flex matching, an algorithm using multiple rounds of control selection with successively relaxed matching criteria to select controls for cases.

Methods: We simulated exposure-disease relationships in multiple cohort data sets with a range of confounding scenarios and conducted 16,800,000 nested case-control studies, comparing random selection of controls, strict matching, and flex matching.

Multiple types of distress are prospectively associated with increased risk of ovarian cancer.

Background: Few modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co-occurring distress-related factors are associated with ovarian cancer risk.

Association of maternal polygenic risk scores for mental illness with perinatal risk factors for offspring mental illness.

We examined whether genetic risk for mental illness is associated with known perinatal risk factors for offspring mental illness to determine whether gene-environmental correlation might account for the associations of perinatal factors with mental illness. Among 8983 women with 19,733 pregnancies, we found that genetic risk for mental illness was associated with any smoking during pregnancy [attention-deficit hyperactivity disorder (ADHD) and overall genetic risk], breast-feeding for less than 1 month (ADHD, depression, and overall genetic risk), experience of intimate partner violence in the year before the birth (depression and overall genetic risk), and pregestational overweight or obesity (bipolar disorder). These results indicate that genetic risk may partly account for the association between perinatal conditions and mental illness in offspring.

Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry.

Trauma, psychological distress and markers of systemic inflammation among US women: A longitudinal study.

Background: Prior evidence links posttraumatic stress disorder (PTSD) and depression, separately, with chronic inflammation. However, whether effects are similar across each independently or potentiated when both are present is understudied. We evaluated combined measures of PTSD and depression in relation to inflammatory biomarker concentrations.

Posttraumatic Stress Disorder, Depression, and Accelerated Aging: Leukocyte Telomere Length in the Nurses' Health Study II.

Background: Exposure to trauma, posttraumatic stress disorder (PTSD), and depression have been independently associated with leukocyte telomere length (LTL), a cellular marker of aging associated with mortality and age-related diseases. However, the joint contributions of trauma and its psychological sequelae on LTL have not been examined.

Methods: We conducted an analysis of LTL in a subset of women from the Nurses' Health Study II ( = 1868).

Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress.

Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment.

Trauma, Post-Traumatic Stress Disorder, and Treatment Among Middle-Aged and Older Women in the Nurses' Health Study II.

Objective: Trauma and post-traumatic stress disorder (PTSD) are common among women and associated with negative health outcomes across the life course. Relatively few studies, however, have examined the epidemiology of trauma, PTSD, and treatment among middle-aged and older civilian women, who are at elevated risk for adverse health outcomes. We aimed to characterize trauma, PTSD, and trauma-related treatment prevalence and correlates in a large cohort of middle-aged and older women.

The impact of psychopathology, social adversity and stress-relevant DNA methylation on prospective risk for post-traumatic stress: A machine learning approach.

Background: A range of factors have been identified that contribute to greater incidence, severity, and prolonged course of post-traumatic stress disorder (PTSD), including: comorbid and/or prior psychopathology; social adversity such as low socioeconomic position, perceived discrimination, and isolation; and biological factors such as genomic variation at glucocorticoid receptor regulatory network (GRRN) genes. This complex etiology and clinical course make identification of people at higher risk of PTSD challenging. Here we leverage machine learning (ML) approaches to identify a core set of factors that may together predispose persons to PTSD.

Polygenic risk for autism, attention-deficit hyperactivity disorder, schizophrenia, major depressive disorder, and neuroticism is associated with the experience of childhood abuse.

People who experience childhood abuse are at increased risk of mental illness. Twin studies suggest that inherited genetic risk for mental illness may account for some of these associations. Yet, the hypothesis that individuals who have experienced childhood abuse may carry genetic loading for mental illness has never been tested with genetic data.

Posttraumatic Stress Disorder and Likelihood of Hormone Therapy Use among Women in the Nurses' Health Study II: A 26-Year Prospective Analysis.

Background: Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. Although prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use. We examined whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years.

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

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.

An Exposure-Wide and Mendelian Randomization Approach to Identifying Modifiable Factors for the Prevention of Depression.

Objective: Efforts to prevent depression, the leading cause of disability worldwide, have focused on a limited number of candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank participants, the authors sought to systematically screen and validate a wide range of potential modifiable factors for depression.

Methods: Baseline data were extracted for 106 modifiable factors, including lifestyle (e.

Correction to: Evaluating a screener to quantify PTSD risk using emergency care information: a proof of concept study.

An amendment to this paper has been published and can be accessed via the original article.