| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Bryazka, D., et al.
(författare)
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Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10347, s. 185-235
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Tidskriftsartikel (refereegranskat)abstract
- Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 3. |
- Pagnamenta, A. T., et al.
(författare)
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An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144, s. 584-600
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Tidskriftsartikel (refereegranskat)abstract
- The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose 47000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 +/- 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.
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| 4. |
- Abah, SE, et al.
(författare)
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Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 17527-
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Tidskriftsartikel (refereegranskat)abstract
- Severe Malarial Anemia (SMA), a life-threatening childhood Plasmodium falciparum malaria syndrome requiring urgent blood transfusion, exhibits inflammatory and hemolytic pathology. Differentiating between hypo-haptoglobinemia due to hemolysis or that of genetic origin is key to understand SMA pathogenesis. We hypothesized that while malaria-induced hypo-haptoglobinemia should reverse at recovery, that of genetic etiology should not. We carried-out a case-control study of children living under hyper-endemic holoendemic malaria burden in the sub-Saharan metropolis of Ibadan, Nigeria. We show that hypo-haptoglobinemia is a risk factor for childhood SMA and not solely due to intravascular hemolysis from underlying schizogony. In children presenting with SMA, hypo-haptoglobinemia remains through convalescence to recovery suggesting a genetic cause. We identified a haptoglobin gene variant, rs12162087 (g.-1203G > A, frequency = 0.67), to be associated with plasma haptoglobin levels (p = 8.5 × 10−6). The Homo-Var:(AA) is associated with high plasma haptoglobin while the reference Homo-Ref:(GG) is associated with hypo-haptoglobinemia (p = 2.3 × 10−6). The variant is associated with SMA, with the most support for a risk effect for Homo-Ref genotype. Our insights on regulatory haptoglobin genotypes and hypo-haptoglobinemia suggest that haptoglobin screening could be part of risk-assessment algorithms to prevent rapid disease progression towards SMA in regions with no-access to urgent blood transfusion where SMA accounts for high childhood mortality rates.
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| 5. |
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| 6. |
- Kousathanas, A, et al.
(författare)
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Whole-genome sequencing reveals host factors underlying critical COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 607:7917, s. 97-
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Tidskriftsartikel (refereegranskat)abstract
- Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
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| 7. |
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| 8. |
- Dierckens, M., et al.
(författare)
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National-Level Wealth Inequality and Socioeconomic Inequality in Adolescent Mental Well-Being : A Time Series Analysis of 17 Countries
- 2020
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Ingår i: Journal of Adolescent Health. - : Elsevier. - 1054-139X .- 1879-1972. ; 66:6, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Although previous research has established a positive association between national income inequality and socioeconomic inequalities in adolescent health, very little is known about the extent to which national-level wealth inequalities (i.e., accumulated financial resources) are associated with these inequalities in health. Therefore, this study examined the association between national wealth inequality and income inequality and socioeconomic inequality in adolescents' mental well-being at the aggregated level. Methods: Data were from 17 countries participating in three consecutive waves (2010, 2014, and 2018) of the cross-sectional Health Behaviour in School-aged Children study. We aggregated data on adolescents' life satisfaction, psychological and somatic symptoms, and socioeconomic status (SES) to produce a country-level slope index of inequality and combined it with country-level data on income inequality and wealth inequality (n = 244,771). Time series analyses were performed on a pooled sample of 48 country-year groups. Results: Higher levels of national wealth inequality were associated with fewer average psychological and somatic symptoms, while higher levels of national income inequality were associated with more psychological and somatic symptoms. No associations between either national wealth inequality or income inequality and life satisfaction were found. Smaller differences in somatic symptoms between higher and lower SES groups were found in countries with higher levels of national wealth inequality. In contrast, larger differences in psychological symptoms and life satisfaction (but not somatic symptoms) between higher and lower SES groups were found in countries with higher levels of national income inequality. Conclusions: Although both national wealth and income inequality are associated with socioeconomic inequalities in adolescent mental well-being at the aggregated level, associations are in opposite directions. Social policies aimed at a redistribution of income resources at the national level could decrease socioeconomic inequalities in adolescent mental well-being while further research is warranted to gain a better understanding of the role of national wealth inequality in socioeconomic inequalities in adolescent health.
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| 9. |
- Dierckens, M., et al.
(författare)
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National level wealth inequality and socioeconomic inequality in adolescent mental wellbeing
- 2020
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 30:Supplement 5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious research established a positive association between national income inequality and socioeconomic inequalities in adolescent health, but little is known about the extent to which national level inequalities in accumulated financial resources (i.e. wealth) are associated with these health inequalities. Therefore, we examined the association between national wealth inequality and income inequality and socioeconomic inequalities in adolescent mental wellbeing.MethodsData were from 17 countries participating in three successive waves (2010, 2014 and 2018) of the cross-sectional Health Behaviour in School-aged Children (HBSC) study. We combined individual-level data on adolescents' life satisfaction, psychological and somatic symptoms and socioeconomic status (SES) with country-level data on income and wealth inequality (n = 244771). We performed time-series analysis on a pooled sample of 48 country/year groups.ResultsHigher levels of national wealth inequality were associated with fewer average psychological and somatic symptoms, while higher levels of national income inequality were associated with more psychological and somatic symptoms. No associations between either national wealth inequality or income inequality and life satisfaction were found. Smaller differences in somatic symptoms between higher and lower SES groups were found in countries with higher levels of national wealth inequality. In contrast, larger differences in psychological symptoms and life satisfaction (but not somatic symptoms) between higher and lower SES groups were found in countries with higher levels of national income inequality.ConclusionsAlthough both national wealth and income inequality are associated with (socioeconomic inequalities in) adolescent mental wellbeing, associations are in opposite directions. Further research is warranted to gain better understanding in the role of national wealth inequality on (socioeconomic inequalities in) adolescent health.Key MessagesThis is one of the first studies to examine if socioeconomic inequalities in adolescent mental wellbeing are associated with national wealth inequality independently from national income inequality.Opposing effects of national wealth inequality and income inequality on socioeconomic inequalities in adolescents’ mental wellbeing warrant further research before policy recommendations can be made.
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