Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

BACKGROUND: Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study.METHODS: We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R 2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. FINDINGS: Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R 2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. INTERPRETATION: These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity.FUNDING: Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.</p

Psychosocial Factors Associated with Patterns of Smoking Surrounding Pregnancy in Fragile Families

Although research has documented factors associated with maternal smoking, we need a more in-depth understanding of the risk factors associated with changes in smoking behaviors during the postpartum period. We investigate smoking patterns during pregnancy and 1 year postpartum as a function of relevant psychosocial factors. We use data on 3,522 postpartum mothers from the Fragile Families and Child Wellbeing Study to analyze the predictors of smoking among mothers who did not smoke during pregnancy but smoked at 1 year postpartum, mothers who smoked both during pregnancy and postpartum, and mothers who did not smoke during either period. Our covariates are grouped into four categories of risk factors for smoking: socioeconomic status, health care, life course and health, and partner and social support. Postpartum mothers in our sample were more likely to smoke throughout or after their pregnancies if they had only a high school education or less, had a household income three or more times below the poverty line, had public or no health insurance, breastfed for less than 5 months, were not married to the infant’s father, if the infant’s father currently smoked, and if they attended religious services less than once a week. Mental health problems were consistently associated with an increased risk of constant and postpartum smoking relative to non-smoking. Psychosocial factors play a role in postpartum smoking, but they have a stronger effect in predicting smoking that persists throughout pregnancy and the first year postpartum

Birds and bioenergy within the americas: A cross‐national, social–ecological study of ecosystem service tradeoffs

Although renewable energy holds great promise in mitigating climate change, there are socioeconomic and ecological tradeoffs related to each form of renewable energy. Forest‐related bioenergy is especially controversial, because tree plantations often replace land that could be used to grow food crops and can have negative impacts on biodiversity. In this study, we examined public perceptions and ecosystem service tradeoffs between the provisioning services associated with cover types associated with bioenergy crop (feedstock) production and forest habitat‐related supporting services for birds, which themselves provide cultural and regulating services. We combined a social survey‐based assessment of local values and perceptions with measures of bioenergy feedstock production impacts on bird habitat in four countries: Argentina, Brazil, Mexico, and the USA. Respondents in all countries rated birds as important or very important (83–99% of respondents) and showed lower enthusiasm for, but still supported, the expansion of bioenergy feedstocks (48–60% of respondents). Bioenergy feedstock cover types in Brazil and Argentina had the greatest negative impact on birds but had a positive impact on birds in the USA. In Brazil and Mexico, public perceptions aligned fairly well with the realities of the impacts of potential bioenergy feedstocks on bird communities. However, in Argentina and the USA, perceptions of bioenergy impacts on birds did not match well with the data. Understanding people’s values and perceptions can help inform better policy and management decisions regarding land use changes

A multilevel examination of gender differences in the association between features of the school environment and physical activity among a sample of grades 9 to 12 students in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Creating school environments that support student physical activity (PA) is a key recommendation of policy-makers to increase youth PA. Given males are more active than females at all ages, it has been suggested that investigating gender differences in the features of the environment that associate with PA may help to inform gender-focused PA interventions and reduce the gender disparity in PA. The purpose of this cross-sectional study was to explore gender differences in the association between factors of the school environment and students' time spent in PA.</p> <p>Methods</p> <p>Among a sample of 10781 female and 10973 male students in grades 9 to 12 from 76 secondary schools in Ontario, Canada, student- and school-level survey PA data were collected and supplemented with GIS-derived measures of the built environment within 1-km buffers of the 76 schools.</p> <p>Results</p> <p>Findings from the present study revealed significant differences in the time male and female students spent in PA as well as in some of the school- and student-level factors associated with PA. Results of the gender-specific multilevel analyses indicate schools should consider providing an alternate room for PA, especially for providing flexibility activities directed at female students. Schools should also consider offering daily physical education programming to male students in senior grades and providing PA promotion initiatives targeting obese male students.</p> <p>Conclusions</p> <p>Although most variation in male and female students' time spent in PA lies between students within schools, there is sufficient between-school variation to be of interest to practitioners and policy-makers. More research investigating gender differentials in environment factors associated with youth PA are warranted.</p

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

Aim: Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location: Global. Methods: We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results: Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions: Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.Fil: Kot, Connie Y.. University of Duke; Estados UnidosFil: Åkesson, Susanne. Lund University; SueciaFil: Alfaro Shigueto, Joanna. Universidad Cientifica del Sur; Perú. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Amorocho Llanos, Diego Fernando. Research Center for Environmental Management and Development; ColombiaFil: Antonopoulou, Marina. Emirates Wildlife Society-world Wide Fund For Nature; Emiratos Arabes UnidosFil: Balazs, George H.. Noaa Fisheries Service; Estados UnidosFil: Baverstock, Warren R.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Blumenthal, Janice M.. Cayman Islands Government; Islas CaimánFil: Broderick, Annette C.. University of Exeter; Reino UnidoFil: Bruno, Ignacio. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Canbolat, Ali Fuat. Hacettepe Üniversitesi; Turquía. Ecological Research Society; TurquíaFil: Casale, Paolo. Università degli Studi di Pisa; ItaliaFil: Cejudo, Daniel. Universidad de Las Palmas de Gran Canaria; EspañaFil: Coyne, Michael S.. Seaturtle.org; Estados UnidosFil: Curtice, Corrie. University of Duke; Estados UnidosFil: DeLand, Sarah. University of Duke; Estados UnidosFil: DiMatteo, Andrew. CheloniData; Estados UnidosFil: Dodge, Kara. New England Aquarium; Estados UnidosFil: Dunn, Daniel C.. University of Queensland; Australia. The University of Queensland; Australia. University of Duke; Estados UnidosFil: Esteban, Nicole. Swansea University; Reino UnidoFil: Formia, Angela. Wildlife Conservation Society; Estados UnidosFil: Fuentes, Mariana M. P. B.. Florida State University; Estados UnidosFil: Fujioka, Ei. University of Duke; Estados UnidosFil: Garnier, Julie. The Zoological Society of London; Reino UnidoFil: Godfrey, Matthew H.. North Carolina Wildlife Resources Commission; Estados UnidosFil: Godley, Brendan J.. University of Exeter; Reino UnidoFil: González Carman, Victoria. Instituto National de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Harrison, Autumn Lynn. Smithsonian Institution; Estados UnidosFil: Hart, Catherine E.. Grupo Tortuguero de las Californias A.C; México. Investigacion, Capacitacion y Soluciones Ambientales y Sociales A.C; MéxicoFil: Hawkes, Lucy A.. University of Exeter; Reino UnidoFil: Hays, Graeme C.. Deakin University; AustraliaFil: Hill, Nicholas. The Zoological Society of London; Reino UnidoFil: Hochscheid, Sandra. Stazione Zoologica Anton Dohrn; ItaliaFil: Kaska, Yakup. Dekamer—Sea Turtle Rescue Center; Turquía. Pamukkale Üniversitesi; TurquíaFil: Levy, Yaniv. University Of Haifa; Israel. Israel Nature And Parks Authority; IsraelFil: Ley Quiñónez, César P.. Instituto Politécnico Nacional; MéxicoFil: Lockhart, Gwen G.. Virginia Aquarium Marine Science Foundation; Estados Unidos. Naval Facilities Engineering Command; Estados UnidosFil: López-Mendilaharsu, Milagros. Projeto TAMAR; BrasilFil: Luschi, Paolo. Università degli Studi di Pisa; ItaliaFil: Mangel, Jeffrey C.. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Margaritoulis, Dimitris. Archelon; GreciaFil: Maxwell, Sara M.. University of Washington; Estados UnidosFil: McClellan, Catherine M.. University of Duke; Estados UnidosFil: Metcalfe, Kristian. University of Exeter; Reino UnidoFil: Mingozzi, Antonio. Università Della Calabria; ItaliaFil: Moncada, Felix G.. Centro de Investigaciones Pesqueras; CubaFil: Nichols, Wallace J.. California Academy Of Sciences; Estados Unidos. Center For The Blue Economy And International Environmental Policy Program; Estados UnidosFil: Parker, Denise M.. Noaa Fisheries Service; Estados UnidosFil: Patel, Samir H.. Coonamessett Farm Foundation; Estados Unidos. Drexel University; Estados UnidosFil: Pilcher, Nicolas J.. Marine Research Foundation; MalasiaFil: Poulin, Sarah. University of Duke; Estados UnidosFil: Read, Andrew J.. Duke University Marine Laboratory; Estados UnidosFil: Rees, ALan F.. University of Exeter; Reino Unido. Archelon; GreciaFil: Robinson, David P.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Robinson, Nathan J.. Fundación Oceanogràfic; EspañaFil: Sandoval-Lugo, Alejandra G.. Instituto Politécnico Nacional; MéxicoFil: Schofield, Gail. Queen Mary University of London; Reino UnidoFil: Seminoff, Jeffrey A.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Seney, Erin E.. University Of Central Florida; Estados UnidosFil: Snape, Robin T. E.. University of Exeter; Reino UnidoFil: Sözbilen, Dogan. Dekamer—sea Turtle Rescue Center; Turquía. Pamukkale University; TurquíaFil: Tomás, Jesús. Institut Cavanilles de Biodiversitat I Biologia Evolutiva; EspañaFil: Varo Cruz, Nuria. Universidad de Las Palmas de Gran Canaria; España. Ads Biodiversidad; España. Instituto Canario de Ciencias Marinas; EspañaFil: Wallace, Bryan P.. University of Duke; Estados Unidos. Ecolibrium, Inc.; Estados UnidosFil: Wildermann, Natalie E.. Texas A&M University; Estados UnidosFil: Witt, Matthew J.. University of Exeter; Reino UnidoFil: Zavala Norzagaray, Alan A.. Instituto politecnico nacional; MéxicoFil: Halpin, Patrick N.. University of Duke; Estados Unido

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species.

In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven\u27t been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies