| 1. |
- Porcu, E, et al.
(författare)
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Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3300-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits.
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| 2. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 3. |
- Luyssaert, S, et al.
(författare)
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The European land and inland water CO2, CO, CH4 and N2O balance between 2001 and 2005
- 2012
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Ingår i: Biogeosciences. - : European Geosciences Union (EGU) / Copernicus Publications. - 1726-4170 .- 1726-4189. ; 9:8, s. 3357-3380
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Tidskriftsartikel (refereegranskat)abstract
- Globally, terrestrial ecosystems have absorbed about 30% of anthropogenic greenhouse gas emissions over the period 2000-2007 and inter-hemispheric gradients indicate that a significant fraction of terrestrial carbon sequestration must be north of the Equator. We present a compilation of the CO2, CO, CH4 and N2O balances of Europe following a dual constraint approach in which (1) a land-based balance derived mainly from ecosystem carbon inventories and (2) a land-based balance derived from flux measurements are compared to (3) the atmospheric data-based balance derived from inversions constrained by measurements of atmospheric GHG (greenhouse gas) concentrations. Good agreement between the GHG balances based on fluxes (1294 +/- 545 Tg C in CO2-eq yr(-1)), inventories (1299 +/- 200 Tg C in CO2-eq yr(-1)) and inversions (1210 +/- 405 Tg C in CO2-eq yr(-1)) increases our confidence that the processes underlying the European GHG budget are well understood and reasonably sampled. However, the uncertainty remains large and largely lacks formal estimates. Given that European net land to atmosphere exchanges are determined by a few dominant fluxes, the uncertainty of these key components needs to be formally estimated before efforts could be made to reduce the overall uncertainty. The net land-to-atmosphere flux is a net source for CO2, CO, CH4 and N2O, because the anthropogenic emissions by far exceed the biogenic sink strength. The dual-constraint approach confirmed that the European biogenic sink removes as much as 205 +/- 72 Tg C yr(-1) from fossil fuel burning from the atmosphere. However, This C is being sequestered in both terrestrial and inland aquatic ecosystems. If the C-cost for ecosystem management is taken into account, the net uptake of ecosystems is estimated to decrease by 45% but still indicates substantial C-sequestration. However, when the balance is extended from CO2 towards the main GHGs, C-uptake by terrestrial and aquatic ecosystems is offset by emissions of non-CO2 GHGs. As such, the European ecosystems are unlikely to contribute to mitigating the effects of climate change.
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| 4. |
- Kolipakam, Vishnupriya, et al.
(författare)
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A Bayesian phylogenetic study of the Dravidian language family
- 2018
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Ingår i: Royal Society Open Science. - : ROYAL SOC. - 2054-5703. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- The Dravidian language family consists of about 80 varieties (Hammarstrom H. 2016 Glottolog 2.7) spoken by 220 million people across southern and central India and surrounding countries (Steever SB. 1998 Tn The Dravidian languages (ed. SB Steever), pp. 1-39: 1). Neither the geographical origin of the Dravidian language homeland nor its exact dispersal through time are known. The history of these languages is crucial for understanding prehistory in Eurasia, because despite their current restricted range, these languages played a significant role in influencing other language groups including IndoAryan (Indo-European) and Munda (Austroasiatic) speakers. Here, we report the results of a Bayesian phylogenetic analysis of cognate -coded lexical data, elicited first hand from native speakers, to investigate the subgrouping of the Dravidian language family, and provide dates for the major points of diversification. Our results indicate that the Dravidian language family is approximately 4500 years old, a finding that corresponds well with earlier linguistic and archaeological studies. The main branches of the Dravidian language family (North, Central, South I, South II) are recovered, although the placement of languages within these main branches diverges from previous classifications. We find considerable uncertainty with regard to the relationships between the main branches.
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| 5. |
- Kronenberg, Linda M., et al.
(författare)
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Personal Recovery in Individuals Diagnosed with Substance use Disorder (SUD) and Co-Occurring Attention Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder (ASD)
- 2015
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Ingår i: Archives of Psychiatric Nursing. - : Elsevier BV. - 0883-9417 .- 1532-8228. ; 29:4, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- The process of personal recovery in people diagnosed with substance use disorder and comorbid attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) was mapped. Four general themes representing four consecutive stages in the recovery process were identified in both client groups: (1) crisis and diagnosis; (2) dealing with agitation, symptoms, and burden; (3) reorganization of life; and (4) meaningful life. However, the personal recovery outcomes and the need for support were different for the two clients groups. Based on these findings, mental health nurses can offer recovery supporting care tailored to the challenging needs of these clients. For the SUD + ADHD group, overall, a coaching attitude is preferred. For the SUD + ASD group, overall, instructional, supportive and directive attitude is needed.
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| 6. |
- Morberg Jämterud, Sofia, PhD, 1977-, et al.
(författare)
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Qualitative study of GPs’ views and experiences of population-based preconception expanded carrier screening in the Netherlands : bioethical perspectives
- 2021
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Ingår i: BMJ Open. - London, United Kingdom : B M J Group. - 2044-6055. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective Between 2016 and 2017, a population-based preconception expanded carrier screening (PECS) test was developed in the Netherlands during a pilot study. It was subsequently made possible in mid-2018 for couples to ask to have such a PECS test from specially trained general practitioners (GPs). Research has described GPs as crucial in offering PECS tests, but little is known about the GPs’ views on PECS and their experiences of providing this test. This article presents a thematic analysis of the PECS practice from the perspective of GPs and a bioethical discussion of the empirical results.Design Empirical bioethics. A thematic analysis of qualitative semi-structured interviews was conducted, and is combined with an ethical/philosophical discussion.Setting The Netherlands.Participants 7 Dutch GPs in the Netherlands, interviewed in 2019–2020.Results Two themes were identified in the thematic analysis: ‘Choice and its complexity’ and ‘PECS as prompting existential concerns’. The empirical bioethics discussion showed that the first theme highlights that several areas coshape the complexity of choice on PECS, and the need for shared relational autonomous decision-making on these areas within the couple. The second theme highlights that it is not possible to analyse the existential issues raised by PECS solely on the level of the couple or family. A societal level must be included, since these levels affect each other. We refer to this as ‘entangled existential genetics’.Conclusion The empirical bioethical analysis leads us to present two practical implications. These are: (1) training of GPs who are to offer PECS should cover shared relational autonomous decision-making within the couple and (2) more attention should be given to existential issues evoked by genetic considerations, also during the education of GPs and in bioethical discussions around PECS.
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| 7. |
- Ormstad, H., et al.
(författare)
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Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders
- 2018
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Ingår i: Cns & Neurological Disorders-Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 17:8, s. 626-639
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). Objective: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. Methods: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP). Results: Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA. Conclusions: Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.
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| 8. |
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| 9. |
- Verkerk, M. A., et al.
(författare)
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Where families and healthcare meet
- 2015
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Ingår i: Journal of Medical Ethics. - : BMJ. - 0306-6800 .- 1473-4257. ; 41:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments in professional healthcare pose moral problems that standard bioethics cannot even identify as problems, but that are fully visible when redefined as problems in the ethics of families. Here, we add to the growing body of work that began in the 1990s by demonstrating the need for a distinctive ethics of families. First, we discuss what 'family' means and why families can matter so deeply to the lives of those within them. Then, we briefly sketch how, according to an ethics of families, responsibilities must be negotiated against the backdrop of family relationships, treatment decisions must be made in the light of these negotiated responsibilities and justice must be served, both between families and society more generally and within families themselves.
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| 10. |
- Verner-Carlsson, Jenny, et al.
(författare)
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First evidence of Seoul hantavirus in the wild rat population in the Netherlands
- 2015
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Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 5, s. 27215-
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of Seoul hantavirus (SEOV)-specific antibodies in the wild brown rat population in the Netherlands. SEOV-reactive antibodies were found in three rats out of 16 in a repeated series of tests including immunofluorescence assay, immunoblot, and enzyme-linked immunosorbent assay. Focus reduction neutralization test confirmed the presence of SEOV-specific antibodies, and reverse-transcription polymerase chain reaction (RT-PCR) confirmed the presence of hantaviral RNA. This discovery follows the recent findings of SEOV infections in wild and pet brown rats and humans in England, Wales, France, Belgium, and Sweden, indicating an even higher importance of this hantavirus for public health in large areas of Europe.
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