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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Arnau-Soler, A, et al.
(författare)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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- Jackson, D, et al.
(författare)
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Closing the know-do gap for child health: UNICEF's experiences from embedding implementation research in child health and nutrition programming
- 2021
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Ingår i: Implementation science communications. - : Springer Science and Business Media LLC. - 2662-2211. ; 2:1, s. 112-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- UNICEF operates in 190 countries and territories, where it advocates for the protection of children’s rights and helps meet children’s basic needs to reach their full potential. Embedded implementation research (IR) is an approach to health systems strengthening in which (a) generation and use of research is led by decision-makers and implementers; (b) local context, priorities, and system complexity are taken into account; and (c) research is an integrated and systematic part of decision-making and implementation. By addressing research questions of direct relevance to programs, embedded IR increases the likelihood of evidence-informed policies and programs, with the ultimate goal of improving child health and nutrition.This paper presents UNICEF’s embedded IR approach, describes its application to challenges and lessons learned, and considers implications for future work.From 2015, UNICEF has collaborated with global development partners (e.g. WHO, USAID), governments and research institutions to conduct embedded IR studies in over 25 high burden countries. These studies focused on a variety of programs, including immunization, prevention of mother-to-child transmission of HIV, birth registration, nutrition, and newborn and child health services in emergency settings. The studies also used a variety of methods, including quantitative, qualitative and mixed-methods.UNICEF has found that this systematically embedding research in programs to identify implementation barriers can address concerns of implementers in country programs and support action to improve implementation. In addition, it can be used to test innovations, in particular applicability of approaches for introduction and scaling of programs across different contexts (e.g., geographic, political, physical environment, social, economic, etc.). UNICEF aims to generate evidence as to what implementation strategies will lead to more effective programs and better outcomes for children, accounting for local context and complexity, and as prioritized by local service providers. The adaptation of implementation research theory and practice within a large, multi-sectoral program has shown positive results in UNICEF-supported programs for children and taking them to scale.
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- Kraef, PC, et al.
(författare)
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Primary health care and nutrition
- 2020
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Ingår i: Bulletin of the World Health Organization. - 1564-0604. ; 98:12, s. 886-893
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Tidskriftsartikel (refereegranskat)
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- Voss, ML, et al.
(författare)
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The missing middle of childhood
- 2023
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Ingår i: Global health action. - 1654-9880. ; 16:1, s. 2242196-
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Tidskriftsartikel (refereegranskat)
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| 40. |
- Waiswa, P, et al.
(författare)
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Child health and the implementation of Community and District-management Empowerment for Scale-up (CODES) in Uganda: a randomised controlled trial
- 2021
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Uganda’s district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.MethodsA 3-year randomised controlled trial (RCT) comprised of 16 Ugandan districts tested a management approach, Community and District-management Empowerment for Scale-up (CODES). Eight districts were randomly selected for each of the intervention and comparison areas. The approach relies on a customised set of data-driven diagnostic tools to identify and resolve health system bottlenecks. Using a difference-in-differences approach, the authors performed an intention-to-treat analysis of protective, preventive and curative practices for malaria, pneumonia and diarrhoea among children aged 5 and younger.ResultsIntervention districts reported significant net increases in the treatment of malaria (+23%), pneumonia (+19%) and diarrhoea (+13%) and improved stool disposal (+10%). Coverage rates for immunisation and vitamin A consumption saw similar improvements. By engaging communities and district managers in a common quest to solve local bottlenecks, CODES fostered demand for health services. However, limited fiscal space-constrained district managers’ ability to implement solutions identified through CODES.ConclusionData-driven district management interventions can positively impact child health outcomes, with clinically significant improvements in the treatment of malaria, pneumonia and diarrhoea as well as stool disposal. The findings recommend the model’s suitability for health systems strengthening in Uganda and other decentralised contexts.Trial registration numberISRCTN15705788.
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