| 1. |
- Estrada, Karol, et al.
(författare)
-
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
|
|
| 2. |
- Halonen, Jaana I., et al.
(författare)
-
Psychological distress and sickness absence : Within- versus between-individual analysis
- 2020
-
Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 264, s. 333-339
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Uncertainty remains whether associations for psychological distress and sickness absence (SA) observed between and within individuals differ, and whether age, gender and work-related factors moderate these associations.Methods: We analyzed SA records of 41,184 participants of the Finnish Public Sector study with repeated survey data between 2000 and 2016 (119,024 observations). Psychological distress was measured by the General Health Questionnaire (GHQ-12), while data on SA days were from the employers' registers. We used a hybrid regression estimation approach adjusting for time-variant confounders-age, marital status, occupational class, body mass index, job contract type, months worked in the follow-up year, job demand, job control, and workplace social capital-and time-invariant gender (for between-individual analysis).Results: Higher levels of psychological distress were consistently associated with SA, both within- and between-individuals. The within-individual association (incidence rate ratio (IRR) 1.68, 95% CI 1.61-1.75 for SA at high distress), however, was substantially smaller than the between-individual association (IRR 2.53, 95% CI 2.39-2.69). High levels of psychological distress had slightly stronger within-individual associations with SA among older (>45 years) than younger employees, lower than higher occupational class, and among men than women. None of the assessed work unit related factors (e.g. job demand, job control) were consistent moderators.Limitations: These findings may not be generalizable to other working sectors or cultures with different SA policies or study populations that are male dominated.Conclusions: Focus on within-individual variation over time provides more accurate estimates of the contribution of mental health to subsequent sickness absence.
|
|
| 3. |
- Halonen, Jaana, et al.
(författare)
-
Psychotropic medication before and after disability retirement by pre-retirement perceived work-related stress
- 2020
-
Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 30:1, s. 158-163
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Retirement has been associated with improved mental health, but it is unclear how much this is due to the removal of work-related stressors. We examined rates of psychotropic medication use before and after the transition to disability retirement due to mental, musculoskeletal and other causes by pre-retirement levels of perceived work stress (effort-reward imbalance, ERI). Methods: Register-based date and diagnosis of disability retirement of 2766 participants of the Finnish Public Sector study cohort were linked to survey data on ERI, socialand health-related covariates, and to national records on prescribed reimbursed psychotropic medication, measured as defined daily doses (DDDs). Follow-up for DDDs was 2–5 years before and after disability retirement. We assessed differences in the levels of DDDs before and after retirement among those with high vs. low level of pre-retirement ERI with repeated measures regression. Results: Those with high (vs. low) levels of ERI used slightly more psychotropic medication before disability retirement due to mental disorders [rate ratio (RR) 1.14, 95% confidence intervals (CI) 0.94–1.37], but after retirement this difference attenuated (RR 0.94, 95% CI 0.80–1.10, P for interaction 0.02). Such a change was not observed for the other causes of disability retirement. Conclusions: The level of psychotropic medication use over the transition to disability retirement due to mental, but not musculoskeletal or other, causes was modified by pre-retirement perceived work-related stress. This suggests that among people retiring due to mental disorders those who had stressful jobs benefit from retirement more than those with low levels of work-related stress.
|
|
| 4. |
- Laj, Paolo, et al.
(författare)
-
A global analysis of climate-relevant aerosol properties retrieved from the network of Global Atmosphere Watch (GAW) near-surface observatories
- 2020
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 13:8, s. 4353-4392
-
Tidskriftsartikel (refereegranskat)abstract
- Aerosol particles are essential constituents of the Earth's atmosphere, impacting the earth radiation balance directly by scattering and absorbing solar radiation, and indirectly by acting as cloud condensation nuclei. In contrast to most greenhouse gases, aerosol particles have short atmospheric residence times, resulting in a highly heterogeneous distribution in space and time. There is a clear need to document this variability at regional scale through observations involving, in particular, the in situ near-surface segment of the atmospheric observation system. This paper will provide the widest effort so far to document variability of climate-relevant in situ aerosol properties (namely wavelength dependent particle light scattering and absorption coefficients, particle number concentration and particle number size distribution) from all sites connected to the Global Atmosphere Watch network. High-quality data from almost 90 stations worldwide have been collected and controlled for quality and are reported for a reference year in 2017, providing a very extended and robust view of the variability of these variables worldwide. The range of variability observed worldwide for light scattering and absorption coefficients, single-scattering albedo, and particle number concentration are presented together with preliminary information on their long-term trends and comparison with model simulation for the different stations. The scope of the present paper is also to provide the necessary suite of information, including data provision procedures, quality control and analysis, data policy, and usage of the ground-based aerosol measurement network. It delivers to users of the World Data Centre on Aerosol, the required confidence in data products in the form of a fully characterized value chain, including uncertainty estimation and requirements for contributing to the global climate monitoring system.
|
|
| 5. |
- Leinonen, Ville, et al.
(författare)
-
Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B.
- 2008
-
Ingår i: Archives of Neurology. - : American Medical Association (AMA). - 0003-9942 .- 1538-3687. ; 65:10, s. 1304-9
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) findings in patients with and without Alzheimer disease lesions in frontal cortical biopsy specimens.DESIGN: Cross-sectional study of [11C]PiB PET findings in patients with or without beta-amyloid (Abeta) aggregates in frontal cortical biopsy specimens.SETTING: Two university hospitals in Finland. Patients Ten patients who had undergone intraventricular pressure monitoring with a frontal cortical biopsy (evaluated for Abeta aggregates and hyperphosphorylated tau) for suspected normal-pressure hydrocephalus.INTERVENTIONS: [11C]PiB PET and evaluation for cognitive impairment using a battery of neuropsychological tests.MAIN OUTCOME MEASURES: Immunohistochemical evaluation for Abeta aggregates and hyperphosphorylated tau in the frontal cortical biopsy specimen and [11C]PiB PET.RESULTS: In patients with Abeta aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [11C]PiB uptake (P < .05) in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal Abeta deposits.CONCLUSIONS: Our study supports the use of noninvasive [11C]PiB PET in the assessment of Abeta deposition in the brain. Large prospective studies are required to verify whether [11C]PiB PET will be a diagnostic aid, particularly in early Alzheimer disease.
|
|
| 6. |
- Nieminen, Tuomo, et al.
(författare)
-
Global analysis of continental boundary layer new particle formation based on long-term measurements
- 2018
-
Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:19, s. 14737-14756
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric new particle formation (NPF) is an important phenomenon in terms of global particle number concentrations. Here we investigated the frequency of NPF, formation rates of 10 nm particles, and growth rates in the size range of 10-25 nm using at least 1 year of aerosol number size-distribution observations at 36 different locations around the world. The majority of these measurement sites are in the Northern Hemisphere. We found that the NPF frequency has a strong seasonal variability. At the measurement sites analyzed in this study, NPF occurs most frequently in March-May (on about 30 % of the days) and least frequently in December-February (about 10 % of the days). The median formation rate of 10 nm particles varies by about 3 orders of magnitude (0.01-10 cm(-3) s(-1)) and the growth rate by about an order of magnitude (1-10 nm h(-1)). The smallest values of both formation and growth rates were observed at polar sites and the largest ones in urban environments or anthropogenically influenced rural sites. The correlation between the NPF event frequency and the particle formation and growth rate was at best moderate among the different measurement sites, as well as among the sites belonging to a certain environmental regime. For a better understanding of atmospheric NPF and its regional importance, we would need more observational data from different urban areas in practically all parts of the world, from additional remote and rural locations in North America, Asia, and most of the Southern Hemisphere (especially Australia), from polar areas, and from at least a few locations over the oceans.
|
|
| 7. |
- Pattaro, Cristian, et al.
(författare)
-
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
|
|
| 8. |
- Stenholm, Sari, et al.
(författare)
-
Smoking, physical inactivity and obesity as predictors of healthy and disease-free life expectancy between ages 50 and 75 : a multicohort study
- 2016
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:4, s. 1260-1270
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Smoking, physical inactivity and obesity are modifiable risk factors for morbidity and mortality. The aim of this study was to examine the extent to which the co-occurrence of these behaviour-related risk factors predict healthy life expectancy and chronic disease-free life expectancy in four European cohort studies.METHODS: Data were drawn from repeated waves of four cohort studies in England, Finland, France and Sweden. Smoking status, physical inactivity and obesity (body mass index ≥30 kg/m(2)) were examined separately and in combination. Health expectancy was estimated by using two health indicators: suboptimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years.RESULTS: Compared with men and women with at least two behaviour-related risk factors, those with no behaviour-related risk factors could expect to live on average8 years longer in good health and 6 years longer free of chronic diseases between ages 50 and 75. Having any single risk factor was also associated with reduction in healthy years. No consistent differences between cohorts were observed.CONCLUSIONS: Data from four European countries show that persons with individual and co-occurring behaviour-related risk factors have shorter healthy life expectancy and shorter chronic disease-free life expectancy. Population level reductions in smoking, physical inactivity and obesity could increase life-years lived in good health.
|
|
