In this study we use aggregated weighted scores of environmental effects to study environmental influences on well-being and happiness. To this end, we split a sample of Netherlands Twin Register (NTR) participants into a training (N =4857) and test (N =2077) sample. In the training sample, we use elastic net regression to estimate effect sizes for associations between life satisfaction and two sets of environmental variables: one based on self- report socioenvironmental data, and one based on objective physical environmental data. Based on these effect sizes, we create two poly-environmental scores (PES-S and PES-O, for self-reports and objective data respectively). In the test sample, we perform association analyses between different measures of well-being and the two PESs. We find that the PES-S explains ~36% of the variance in well-being, while the PES-O does not significantly contribute to the model. Variance in other well-being measures (i.e., different life satisfaction domains, subjective happiness, quality of life, flourishing, psychological well-being, self-rated health, depressive problems, and loneliness) are explained to varying extents by the PESs, ranging from 6.36% (self-rated health) to 36.66% (loneliness). These predictive values did not change during the COVID-19 pandemic (N =3214). Validating the PES-S in the UK biobank (N =40,614), we find that the UK biobank PES-S explains about ~12% of the variance in happiness. Lastly, we examine if there is any indication for gene-environment correlation (rGE), the phenomenon where one’s genetic predisposition influences exposure to the environment, by associating the PESs with polygenic scores (PGS) in a sample of Netherlands Twin Register (NTR) and UK Biobank participants. While the PES and PGS were not correlated in the NTR sample, they were correlated in the larger UK biobank sample, indicating the potential presence of rGE. We discuss several limitations pertaining to our dataset, such as a potential influence of common method bias, and reflect on how PESs might be used in future research.
MULTIFILE
The increasing demand for Prunus africana resources is an opportunity for its conservation and commercial use to support livelihoods in Africa. The objective for this study was to investigate major steps to advance production of P. africana for long-term commercial use in Uganda. Specific objectives were to explore potential production schemes, setbacks in production and strategies to advance it. The study was done by review of literature, documents and interviews with experts. Results indicated Agroforestry and large plantations to be useful schemes for production. Identified setbacks are: low trade in P. africana, unknown returns from production, competing land uses, long growth period, limited market assurance and information. The lack of a resource assessment for P. africana in forests contributes to its low trade which undermines related economic benefits for national development and incentives to commercial production. We propose that a national Quantitative resource assessment of P. africana in forests is one of the crucial steps that should be undertaken to carefully organise and advance sustainable trade to provide rational incentives for commercial production. Subsequently, production should be localised in suitable sites and producers be organised into cooperatives. Further research to improve returns from commercial production of P. africana is needed.
MULTIFILE
BackgroundIdentifying modifiable factors associated with well-being is of increased interest for public policy guidance. Developments in record linkage make it possible to identify what contributes to well-being from a myriad of factors. To this end, we link two large-scale data resources; the Geoscience and Health Cohort Consortium, a collection of geo-data, and the Netherlands Twin Register, which holds population-based well-being data.ObjectiveWe perform an Environment-Wide Association Study (EnWAS), where we examine 139 neighbourhood-level environmental exposures in relation to well-being.MethodsFirst, we performed a generalized estimation equation regression (N = 11,975) to test for the effects of environmental exposures on well-being. Second, to account for multicollinearity amongst exposures, we performed principal component regression. Finally, using a genetically informative design, we examined whether environmental exposure is driven by genetic predisposition for well-being.ResultsWe identified 21 environmental factors that were associated with well-being in the domains: housing stock, income, core neighbourhood characteristics, livability, and socioeconomic status. Of these associations, socioeconomic status and safety are indicated as the most important factors to explain differences in well-being. No evidence of gene-environment correlation was found.SignificanceThese observed associations, especially neighbourhood safety, could be informative for policy makers and provide public policy guidance to improve well-being. Our results show that linking databases is a fruitful exercise to identify determinants of mental health that would remain unknown by a more unilateral approach.
Huntington’s disease (HD) and various spinocerebellar ataxias (SCA) are autosomal dominantly inherited neurodegenerative disorders caused by a CAG repeat expansion in the disease-related gene1. The impact of HD and SCA on families and individuals is enormous and far reaching, as patients typically display first symptoms during midlife. HD is characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. SCAs are mainly characterized by ataxia but also other symptoms including cognitive deficits, similarly affecting quality of life and leading to disability. These problems worsen as the disease progresses and affected individuals are no longer able to work, drive, or care for themselves. It places an enormous burden on their family and caregivers, and patients will require intensive nursing home care when disease progresses, and lifespan is reduced. Although the clinical and pathological phenotypes are distinct for each CAG repeat expansion disorder, it is thought that similar molecular mechanisms underlie the effect of expanded CAG repeats in different genes. The predicted Age of Onset (AO) for both HD, SCA1 and SCA3 (and 5 other CAG-repeat diseases) is based on the polyQ expansion, but the CAG/polyQ determines the AO only for 50% (see figure below). A large variety on AO is observed, especially for the most common range between 40 and 50 repeats11,12. Large differences in onset, especially in the range 40-50 CAGs not only imply that current individual predictions for AO are imprecise (affecting important life decisions that patients need to make and also hampering assessment of potential onset-delaying intervention) but also do offer optimism that (patient-related) factors exist that can delay the onset of disease.To address both items, we need to generate a better model, based on patient-derived cells that generates parameters that not only mirror the CAG-repeat length dependency of these diseases, but that also better predicts inter-patient variations in disease susceptibility and effectiveness of interventions. Hereto, we will use a staggered project design as explained in 5.1, in which we first will determine which cellular and molecular determinants (referred to as landscapes) in isogenic iPSC models are associated with increased CAG repeat lengths using deep-learning algorithms (DLA) (WP1). Hereto, we will use a well characterized control cell line in which we modify the CAG repeat length in the endogenous ataxin-1, Ataxin-3 and Huntingtin gene from wildtype Q repeats to intermediate to adult onset and juvenile polyQ repeats. We will next expand the model with cells from the 3 (SCA1, SCA3, and HD) existing and new cohorts of early-onset, adult-onset and late-onset/intermediate repeat patients for which, besides accurate AO information, also clinical parameters (MRI scans, liquor markers etc) will be (made) available. This will be used for validation and to fine-tune the molecular landscapes (again using DLA) towards the best prediction of individual patient related clinical markers and AO (WP3). The same models and (most relevant) landscapes will also be used for evaluations of novel mutant protein lowering strategies as will emerge from WP4.This overall development process of landscape prediction is an iterative process that involves (a) data processing (WP5) (b) unsupervised data exploration and dimensionality reduction to find patterns in data and create “labels” for similarity and (c) development of data supervised Deep Learning (DL) models for landscape prediction based on the labels from previous step. Each iteration starts with data that is generated and deployed according to FAIR principles, and the developed deep learning system will be instrumental to connect these WPs. Insights in algorithm sensitivity from the predictive models will form the basis for discussion with field experts on the distinction and phenotypic consequences. While full development of accurate diagnostics might go beyond the timespan of the 5 year project, ideally our final landscapes can be used for new genetic counselling: when somebody is positive for the gene, can we use his/her cells, feed it into the generated cell-based model and better predict the AO and severity? While this will answer questions from clinicians and patient communities, it will also generate new ones, which is why we will study the ethical implications of such improved diagnostics in advance (WP6).
