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- Jia, TY, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:8, s. 3884-3895
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
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| 9. |
- Ringh, MV, et al.
(författare)
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Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking
- 2021
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 27:7, s. 1014-1026
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Tidskriftsartikel (refereegranskat)abstract
- Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients. Objectives: We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs). Methods: We profiled DNA methylation in BAL cells from female MS ( n = 17) and HC ( n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. Results: The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. Conclusions: Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.
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- Ayoola, A, et al.
(författare)
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Overweight and obesity in south central Uganda: A population-based study
- 2022
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Ingår i: PLOS global public health. - : Public Library of Science (PLoS). - 2767-3375. ; 2:11, s. e0001051-
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a rapidly growing global health challenge, but there are few population-level studies from non-urban settings in sub-Saharan Africa. We evaluated the prevalence of overweight (body mass index (BMI)>25 kg/m2), obesity (BMI>30 kg/m2), and associated factors using data from May 2018 to November 2020 from the Rakai Community Cohort Study, a population-based cohort of residents aged 15 to 49 living in forty-one fishing, trading, and agrarian communities in South Central Uganda. Modified Poisson regression was used to estimate adjusted prevalence risk ratios (PRR) and 95% confidence intervals (CI) in 18,079 participants. The overall mean BMI was 22.9 kg/m2. Mean BMI was 21.5 kg/m2 and 24.1 kg/m2 for males and females, respectively. The prevalence of overweight and obesity were 22.8% and 6.2%, respectively. Females had a higher probability of overweight/obesity (PRR: 4.11, CI: 2.98–5.68) than males. For female participants, increasing age, higher socioeconomic status, residing in a trading or fishing community (PRR: 1.25, CI 1.16–1.35 and PRR: 1.17, CI 1.10–1.25, respectively), being currently or previously married (PRR: 1.22, CI 1.07–1.40 and PRR: 1.16, CI 1.01–1.34, respectively), working in a bar/restaurant (PRR: 1.29, CI 1.17–1.45), trading/shopkeeping (PRR: 1.38, CI 1.29–1.48), and reporting alcohol use in the last year (PRR: 1.21, CI 1.10–1.33) were risk factors for overweight/obese. For male participants, increasing age, higher socioeconomic status, being currently married (PRR: 1.94, CI 1.50–2.50), residing in a fishing community (PRR: 1.68, CI 1.40–2.02), working in a bar/restaurant (PRR: 2.20, CI 1.10–4.40), trading/shopkeeping (PRR: 1.75, CI 1.45–2.11), or fishing (PRR: 1.32, CI 1.03–1.69) increased the probability of overweight/obesity. Non-Muslim participants, male smokers, and HIV-positive females had a lower probability of overweight/obese. The prevalence of overweight/obesity in non-urban Ugandans is substantial. Targeted interventions to high-risk subgroups in this population are needed.
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- Belczynski, K., et al.
(författare)
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Evolutionary roads leading to low effective spins, high black hole masses, and O1/O2 rates for LIGO/Virgo binary black holes
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636:A&A
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Tidskriftsartikel (refereegranskat)abstract
- All ten LIGO/Virgo binary black hole (BH-BH) coalescences reported following the O1/O2 runs have near-zero effective spins. There are only three potential explanations for this. If the BH spin magnitudes are large, then: (i) either both BH spin vectors must be nearly in the orbital plane or (ii) the spin angular momenta of the BHs must be oppositely directed and similar in magnitude. Then there is also the possibility that (iii) the BH spin magnitudes are small. We consider the third hypothesis within the framework of the classical isolated binary evolution scenario of the BH-BH merger formation. We test three models of angular momentum transport in massive stars: A mildly efficient transport by meridional currents (as employed in the Geneva code), an efficient transport by the Tayler-Spruit magnetic dynamo (as implemented in the MESA code), and a very-efficient transport (as proposed by Fuller et al.) to calculate natal BH spins. We allow for binary evolution to increase the BH spins through accretion and account for the potential spin-up of stars through tidal interactions. Additionally, we update the calculations of the stellar-origin BH masses, including revisions to the history of star formation and to the chemical evolution across cosmic time. We find that we can simultaneously match the observed BH-BH merger rate density and BH masses and BH-BH effective spins. Models with efficient angular momentum transport are favored. The updated stellar-mass weighted gas-phase metallicity evolution now used in our models appears to be key for obtaining an improved reproduction of the LIGO/Virgo merger rate estimate. Mass losses during the pair-instability pulsation supernova phase are likely to be overestimated if the merger GW170729 hosts a BH more massive than 50âMâŠ. We also estimate rates of black hole-neutron star (BH-NS) mergers from recent LIGO/Virgo observations. If, in fact. angular momentum transport in massive stars is efficient, then any (electromagnetic or gravitational wave) observation of a rapidly spinning BH would indicate either a very effective tidal spin up of the progenitor star (homogeneous evolution, high-mass X-ray binary formation through case A mass transfer, or a spin-up of a Wolf-Rayet star in a close binary by a close companion), significant mass accretion by the hole, or a BH formation through the merger of two or more BHs (in a dense stellar cluster).
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- Gudmundsdottir, A, et al.
(författare)
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Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012–2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760–6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120–19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740–28,100 ng/L); or surgery, 32,300 ng/L (29,100–35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001–18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54–0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.
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| 18. |
- Jacobs, Susan S., et al.
(författare)
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Home oxygen therapy for adults with chronic lung disease an official american thoracic society clinical practice guideline
- 2020
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 202:10, s. 121-141
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquidoxygen use in patients who are mobile outside the home and require .3 L/min of continuous-flow oxygen during exertion (very-lowquality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (bestpractice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.
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| 19. |
- Maier, AD, et al.
(författare)
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Loss of H3K27me3 in WHO grade 3 meningioma
- 2022
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Ingår i: Brain tumor pathology. - : Springer Science and Business Media LLC. - 1861-387X .- 1433-7398. ; 39:4, s. 200-209
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Xia, CY, et al.
(författare)
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Hodgkin Lymphoma Monozygotic Triplets Reveal Divergences in DNA Methylation Signatures
- 2020
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 10, s. 598872-
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Tidskriftsartikel (refereegranskat)abstract
- We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in naïve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.
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