Home and epigenome: How DNA methylation could explain the association between housing quality and depression

Poor housing quality is a consistent risk factor for mental health problems. Despite the large body of evidence for housing’s relationship with mental health, housing quality as an environmental stressor has not yet been investigated with regards to the mediational process of DNA methylation. Previous investigations have provided little insight into the biological mechanisms through which this association may arise and been limited by insufficient control of socioeconomic status (SES) and baseline depression. By investigating the mediational role of DNA methylation in the association between housing and mental health, this research paper aimed to investigate housing’s potential as both a protectant and opportunity for intervention for mental health on a population-level. In a sample of up to 6,446 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC), we set out to investigate if housing quality (e.g. size, facilities, condensation/mould, decorations and feelings towards the home) associated with depressive symptoms (Crown Crisp Experiential Index depression scores) in early or middle adulthood (mean age 29 and 48, respectively). In these associations we controlled for neighbourhood quality, housing stability (the number of times the individual moved house in the previous 5 years), contextual risk (including socioeconomic factors such as experiences of losing a job, reduced income, homelessness) and familial history of depression (known history of persistent low mood or known diagnoses in parents). We then investigated whether this association was mediated by DNA methylation, measured at the same time points in a sub-sample of these mothers with blood sample data (n=786), whilst controlling for cell-type heterogeneity, total fat-mass, age and smoking. Housing quality predicted depression consistently over 3 years in early adulthood (beta range: .316 to 1.21, all p-values <.003), even after controlling for multiple SES risks, familial depression risk, 5-year housing stability, baseline depression at age 28 and neighbourhood quality. However, housing quality did not predict depression in middle adulthood (beta = 0.63, p value = .251). In an epigenome-wide association analysis (EWAS), housing quality was associated with DNA methylation at 4 CpG sites at age 29 with suggestive evidence for 391 CpGs, as defined in Smith et al. (2021). Following up on these 391 CpGs using high-dimensional mediational analysis, the largest indirect effect, mediating the association between housing and depression at age 29, was detected for a CpG linked to gene SLCO4A1 (beta = -.009, p-value = .052). The smallest indirect effect, mediating the association between housing and depression at age 48, was detected for a CpG linked to gene Mir_544 (beta = -.076, p-value = .037). These results demonstrate the importance of housing quality in depression’s aetiology, especially in early adulthood. However, our findings point towards limited evidence for single CpG sites mediating this association, suggesting a more complex relationship between housing quality, DNA methylation and depression. Moreover, our findings suggest the role of housing quality in the aetiology of depression may vary across the lifespan

A gradient approach to localization of deformation. I. Hyperelastic materials

By utilizing methods recently developed in the theory of fluid interfaces, we provide a new framework for considering the localization of deformation and illustrate it for the case of hyperelastic materials. The approach overcomes one of the major shortcomings in constitutive equations for solids admitting localization of deformation at finite strains, i.e. their inability to provide physically acceptable solutions to boundary value problems in the post-localization range due to loss of ellipticity of the governing equations. Specifically, strain-induced localized deformation patterns are accounted for by adding a second deformation gradient-dependent term to the expression for the strain energy density. The modified strain energy function leads to equilibrium equations which remain always elliptic. Explicit solutions of these equations can be found for certain classes of deformations. They suggest not only the direction but also the width of the deformation bands providing for the first time a predictive unifying method for the study of pre- and post-localization behavior. The results derived here are a three-dimensional extension of certain one-dimensional findings reported earlier by the second author for the problem of simple shear.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42674/1/10659_2004_Article_BF00040814.pd

Coordinated strategy for a model-based decision support tool for coronavirus disease, Utah, USA

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response used in the US state of Utah early in the coronavirus disease pandemic, which brought together a diverse set of technical experts and public health and healthcare officials and led to an evidence-based response to the pandemic. We describe how we adapted a standard epidemiologic model; harmonized the outputs across modeling groups; and maintained a constant dialogue with policymakers at multiple levels of government to produce timely, evidence-based, and coordinated public health recommendations and interventions during the first wave of the pandemic. This framework continues to support the state's response to ongoing outbreaks and can be applied in other settings to address unique public health challenges

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Towards an integrated set of surface meteorological observations for climate science and applications

Observations are the foundation for understanding the climate system. Yet, currently available land meteorological data are highly fractured into various global, regional and national holdings for different variables and timescales, from a variety of sources, and in a mixture of formats. Added to this, many data are still inaccessible for analysis and usage. To meet modern scientific and societal demands as well as emerging needs such as the provision of climate services, it is essential that we improve the management and curation of available land-based meteorological holdings. We need a comprehensive global set of data holdings, of known provenance, that is truly integrated both across Essential Climate Variables (ECVs) and across timescales to meet the broad range of stakeholder needs. These holdings must be easily discoverable, made available in accessible formats, and backed up by multi-tiered user support. The present paper provides a high level overview, based upon broad community input, of the steps that are required to bring about this integration. The significant challenge is to find a sustained means to realize this vision. This requires a long-term international program. The database that results will transform our collective ability to provide societally relevant research, analysis and predictions in many weather and climate related application areas across much of the globe

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes