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| 2. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 3. |
- Howe, LJ, et al.
(författare)
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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:65, s. 581-
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Tidskriftsartikel (refereegranskat)abstract
- Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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| 4. |
- Madsen, I. E. H., et al.
(författare)
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Job strain as a risk factor for clinical depression : systematic review and meta-analysis with additional individual participant data
- 2017
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 47:8, s. 1342-1356
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Forskningsöversikt (refereegranskat)abstract
- Background. Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. Method. We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. Results. We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). Conclusions. Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
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| 5. |
- Nilsson Sommar, Johan, et al.
(författare)
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Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden
- 2021
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate concentration-response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels. Setting Cohorts from Gothenburg, Stockholm and Umea, Sweden. Design High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter <= 10 mu m (PM10) and <= 2.5 mu m (PM2.5), and BC, at individual addresses during each year of follow-up, 1990-2011. Moving averages were calculated for the time windows 1-5 years (lag1-5) and 6-10 years (lag6-10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort. Participants During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up. Results Both PM10 (range: 6.3-41.9 mu g/m(3)) and BC (range: 0.2-6.8 mu g/m(3)) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 mu g/m(3) and 1 mu g/m(3) of lag1-5 exposure, respectively. For PM2.5 (range: 4.0-22.4 mu g/m(3)), the estimated increase was 13% per 5 mu g/m(3), but less precise (95% CI -9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality. Conclusion The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.
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| 6. |
- Cornelissen, Johannes H C, et al.
(författare)
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Global negative vegetation feedback to climate warming responses of leaf litter decomposition rates in cold biomes
- 2007
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 10:7, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Whether climate change will turn cold biomes from large long-term carbon sinks into sources is hotly debated because of the great potential for ecosystem-mediated feedbacks to global climate. Critical are the direction, magnitude and generality of climate responses of plant litter decomposition. Here, we present the first quantitative analysis of the major climate-change-related drivers of litter decomposition rates in cold northern biomes worldwide.Leaf litters collected from the predominant species in 33 global change manipulation experiments in circum-arctic-alpine ecosystems were incubated simultaneously in two contrasting arctic life zones. We demonstrate that longer-term, large-scale changes to leaf litter decomposition will be driven primarily by both direct warming effects and concomitant shifts in plant growth form composition, with a much smaller role for changes in litter quality within species. Specifically, the ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across cold biomes would constitute a negative feedback to global warming. Depending on the strength of other (previously reported) positive feedbacks of shrub expansion on soil carbon turnover, this may partly counteract direct warming enhancement of litter decomposition.
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| 7. |
- Kriit, Hedi Katre, et al.
(författare)
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Using Distributed Lag Non-Linear Models to Estimate Exposure Lag-Response Associations between Long-Term Air Pollution Exposure and Incidence of Cardiovascular Disease
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Long-term air pollution exposure increases the risk for cardiovascular disease, but little is known about the temporal relationships between exposure and health outcomes. This study aims to estimate the exposure-lag response between air pollution exposure and risk for ischemic heart disease (IHD) and stroke incidence by applying distributed lag non-linear models (DLNMs). Annual mean concentrations of particles with aerodynamic diameter less than 2.5 µm (PM2.5 ) and black carbon (BC) were estimated for participants in five Swedish cohorts using dispersion models. Simultaneous estimates of exposure lags 1–10 years using DLNMs were compared with separate year specific (single lag) estimates and estimates for lag 1–5-and 6–10-years using moving average exposure. The DLNM estimated no exposure lag-response between PM2.5 total, BC, and IHD. However, for PM2.5 from local sources, a 20% risk increase per 1 µg/m3 for 1-year lag was estimated. A risk increase for stroke was suggested in relation to lags 2–4-year PM2.5 and BC, and also lags 8–9-years BC. No associations were shown in single lag models. Increased risk estimates for stroke in relation to lag 1–5-and 6–10-years BC moving averages were observed. Estimates generally supported a greater contribution to increased risk from exposure windows closer in time to incident IHD and incident stroke. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 8. |
- Liu, Shuo, et al.
(författare)
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Long-term exposure to low-level air pollution and incidence of asthma : the ELAPSE project
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 mu m (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) with asthma incidence in adults.Methods: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders.Results: Of 98326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 mu g.m(-3) for PM2.5, 1.17 (95% CI 1.10-1.25) per 10 mu g.m(-3) for NO2 and 1.15 (95% CI 1.08-1.23) per 0.5 x 10(-5) m(-1) for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM2.5 and NO2. NO 2 and BC estimates remained unchanged in two-pollutant models with PM2.5, whereas PM2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold.Conclusions: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.
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| 9. |
- Liu, Shuo, et al.
(författare)
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Long-term exposure to low-level air pollution and incidence of chronic obstructive pulmonary disease : The ELAPSE project
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- Background: Air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD), but evidence is sparse and inconsistent.Objectives: We examined the association between long-term exposure to low-level air pollution and COPD incidence.Methods: Within the 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE) study, we pooled data from three cohorts, from Denmark and Sweden, with information on COPD hospital discharge diagnoses. Hybrid land use regression models were used to estimate annual mean concentrations of particulate matter with a diameter < 2.5 mu m (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in 2010 at participants' baseline residential addresses, which were analysed in relation to COPD incidence using Cox proportional hazards models.Results: Of 98,058 participants, 4,928 developed COPD during 16.6 years mean follow-up. The adjusted hazard ratios (HRs) and 95% confidence intervals for associations with COPD incidence were 1.17 (1.06, 1.29) per 5 mu g/m(3) for PM2.5, 1.11 (1.06, 1.16) per 10 mu g/m(3) for NO2, and 1.11 (1.06, 1.15) per 0.5 10(-5) m(-1) for BC. Associations persisted in subset participants with PM2.5 or NO2 levels below current EU and US limit values and WHO guidelines, with no evidence for a threshold. HRs for NO2 and BC remained unchanged in two-pollutant models with PM2.5, whereas the HR for PM2.5 was attenuated to unity with NO2 or BC.Conclusions: Long-term exposure to low-level air pollution is associated with the development of COPD, even below current EU and US limit values and possibly WHO guidelines. Traffic-related pollutants NO2 and BC may be the most relevant.
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| 10. |
- Sørensen, Jeppe K., et al.
(författare)
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Work stress and loss of years lived without chronic disease : an 18-year follow-up of 1.5 million employees in Denmark
- 2022
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:4, s. 389-400
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to examine the association between exposure to work stress and chronic disease incidence and loss of chronic disease-free life years in the Danish workforce. The study population included 1,592,491 employees, aged 30–59 in 2000 and without prevalent chronic diseases. We assessed work stress as the combination of job strain and effort-reward imbalance using job exposure matrices. We used Cox regressions to estimate risk of incident hospital-diagnoses or death of chronic diseases (i.e., type 2 diabetes, coronary heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease, heart failure, and dementia) during 18 years of follow-up and calculated corresponding chronic disease-free life expectancy from age 30 to age 75. Individuals working in occupations with high prevalence of work stress had a higher risk of incident chronic disease compared to those in occupations with low prevalence of work stress (women: HR 1.04 (95% CI 1.02–1.05), men: HR 1.12 (95% CI 1.11–1.14)). The corresponding loss in chronic disease-free life expectancy was 0.25 (95% CI − 0.10 to 0.60) and 0.84 (95% CI 0.56–1.11) years in women and men, respectively. Additional adjustment for health behaviours attenuated these associations among men. We conclude that men working in high-stress occupations have a small loss of years lived without chronic disease compared to men working in low-stress occupations. This finding appeared to be partially attributable to harmful health behaviours. In women, high work stress indicated a very small and statistically non-significant loss of years lived without chronic disease.
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