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The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis.

We present a new approach to constrain and validate atomic oxygen (O) concentrations in the mesopause region (∼ 80 to ∼ 100 km). In a prior companion paper [Mlynczak et al., ], we presented O-atom concentrations in the mesopause region inferred from measurements of day ozone and night hydroxyl emission rates made by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument. The approach presented here uses the constraint of global, annual mean energy balance to derive atomic oxygen concentrations, consistent with rates of radiative cooling by carbon dioxide (CO2) and solar heating due to molecular oxygen (O2). The mathematical difference between these cooling and heating rates, on a global annual mean basis, effectively constrains the maximum heating rate for the sum of all other processes. The remaining terms, solar heating due to ozone plus a series of exothermic chemical reactions can be expressed as functions of O. This new approach enables a simple mathematical expression that yields the vertical profile of global annual mean >radiatively constrained> atomic oxygen in the mesopause region. The radiatively constrained atomic oxygen depends only on the CO2 cooling rates, O2 solar heating rates, and standard reaction rate coefficients and enthalpies. Radiative cooling and solar heating rates used in these analyses are derived from measurements made by the SABER instrument on the NASA Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite. There is excellent agreement between the SABER radiatively constrained atomic oxygen and that derived from the SABER ozone and OH emission measurements over most of the mesopause region. Radiatively constrained atomic oxygen represents an upper limit on the global average O-atom concentration in the mesopause region. © 2013. American Geophysical Union. All Rights Reserved.

Anecdotal evidence suggests that a horse’s prior fitness level has an effect on the horse’s ability to return to that previous level of fitness. This trial aimed to test this assumption which would benefit horse trainers to create individual fitness programs for horses. Standardised exercise testing was used to compare the progress of two groups of horses during weeks three and seven of a 14-week training program. Group A had undergone a similar training program twelve months previously and Group B had not. Plasma lactate samples and heart rate monitoring were used to assess the levels of fitness of the horses. Analysis of variance showed that there was no significant difference in post-exercise plasma lactate concentration between the groups. The horses with previous training experience (Group A) had lower (115.7 v 130.6 bpm) but non-significantly different heart rates than those without previous training experience (Group B) at week 3. This trend did not change after an additional 4 weeks of training (115.5 v 128.4 bpm; Group A and B respectively). Irrespective of training history or speed of each incremental step, there was no improvement in heart rate between week 3 (123.1 bpm) and week 7 (122.0 bpm).