| 1. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 2. |
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| 3. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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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. |
- Dahl, F, et al.
(författare)
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Imaging single DNA molecules for high precision NIPT
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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| 6. |
- Heikkila, Katriina, et al.
(författare)
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Job strain and the risk of inflammatory bowel diseases : individual-participant meta-analysis of 95 000 men and women
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e88711-
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Many clinicians, patients and patient advocacy groups believe stress to have a causal role in inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. However, this is not corroborated by clear epidemiological research evidence. We investigated the association between work-related stress and incident Crohn's disease and ulcerative colitis using individual-level data from 95 000 European adults. Methods: We conducted individual-participant data meta-analyses in a set of pooled data from 11 prospective European studies. All studies are a part of the IPD-Work Consortium. Work-related psychosocial stress was operationalised as job strain (a combination of high demands and low control at work) and was self-reported at baseline. Crohn's disease and ulcerative colitis were ascertained from national hospitalisation and drug reimbursement registers. The associations between job strain and inflammatory bowel disease outcomes were modelled using Cox proportional hazards regression. The study-specific results were combined in random effects meta-analyses. Results: Of the 95 379 participants who were free of inflammatory bowel disease at baseline, 111 men and women developed Crohn's disease and 414 developed ulcerative colitis during follow-up. Job strain at baseline was not associated with incident Crohn's disease (multivariable-adjusted random effects hazard ratio: 0.83, 95% confidence interval: 0.48, 1.43) or ulcerative colitis (hazard ratio: 1.06, 95% CI: 0.76, 1.48). There was negligible heterogeneity among the study-specific associations. Conclusions: Our findings suggest that job strain, an indicator of work-related stress, is not a major risk factor for Crohn's disease or ulcerative colitis.
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| 7. |
- Madsen, Ida E.H., et al.
(författare)
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Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts
- 2014
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Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted "job strain") are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers. The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
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| 8. |
- Syvalahti, EKG, et al.
(författare)
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Citalopram causes no significant alterations in plasma neuroleptic levels in schizophrenic patients
- 1997
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Ingår i: The Journal of international medical research. - : SAGE Publications. - 0300-0605 .- 1473-2300. ; 25:1, s. 24-32
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Tidskriftsartikel (refereegranskat)abstract
- Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of citalopram and its main metabolite, desmethylcitalopram, were also measured. In addition, patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors. There were no significant changes in plasma concentrations of haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or perphenazine during the study. Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy, and remained stable throughout the study. None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that clinically important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients.
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| 9. |
- Theorell, Töres, et al.
(författare)
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Job Strain as a Risk Factor for Type 2 Diabetes : A Pooled Analysis of 124,808 Men and Women
- 2014
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 37:8, s. 2268-2275
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as "job strain," is associated with incident type 2 diabetes independent of lifestyle factors. RESEARCH DESIGN AND METHODS We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses. RESULTS There were 3,703 cases of incident diabetes during a mean follow-up of 10.3 years. After adjustment for age, sex, and socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no job strain was 1.15 (95% CI 1.06-1.25) with no difference between men and women (1.19 [1.06-1.34] and 1.13 [1.00-1.28], respectively). In stratified analyses, job strain was associated with an increased risk of diabetes among those with healthy and unhealthy lifestyle habits. In a multivariable model adjusted for age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00-1.23). CONCLUSIONS Findings from a large pan-European dataset suggest that job strain is a risk factor for type 2 diabetes in men and women independent of lifestyle factors.
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| 10. |
- Virtanen, Marianna, et al.
(författare)
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Long working hours and alcohol use : systematic review and meta-analysis of published studies and unpublished individual participant data.
- 2015
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138. ; 350, s. Art. no. g7772-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To quantify the association between long working hours and alcohol use.DESIGN: Systematic review and meta-analysis of published studies and unpublished individual participant data.DATA SOURCES: A systematic search of PubMed and Embase databases in April 2014 for published studies, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies.REVIEW METHODS: The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were obtained with random effects meta-analysis. Sources of heterogeneity were examined with meta-regression.RESULTS: Cross sectional analysis was based on 61 studies representing 333 693 participants from 14 countries. Prospective analysis was based on 20 studies representing 100 602 participants from nine countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective published and unpublished data. In the 18 studies with individual participant data it was possible to assess the European Union Working Time Directive, which recommends an upper limit of 48 hours a week. Odds ratios of new onset risky alcohol use for those working 49-54 hours and ≥55 hours a week were 1.13 (1.02 to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01 to 1.25; adjusted difference in incidence 0.7 percentage points), respectively, compared with working standard 35-40 hours (incidence of new onset risky alcohol use 6.2%). There was no difference in these associations between men and women or by age or socioeconomic groups, geographical regions, sample type (population based v occupational cohort), prevalence of risky alcohol use in the cohort, or sample attrition rate.CONCLUSIONS: Individuals whose working hours exceed standard recommendations are more likely to increase their alcohol use to levels that pose a health risk.
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| 11. |
- Ahola, Virpi, et al.
(författare)
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The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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| 12. |
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| 13. |
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| 14. |
- Heikkilä, Katriina, et al.
(författare)
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Job strain and COPD exacerbations: an individual-participant meta-analysis
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 247-251
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Tidskriftsartikel (refereegranskat)abstract
- To the Editor:Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and disability worldwide (1). The clinical course of COPD is characterised by exacerbations, which can be minor and manageable at home or in primary care, or severe, leading to hospitalisation or even death. Known causes of exacerbations include tobacco smoke, air pollution, dusts and fumes, and respiratory infections (1, 2). One less well understood risk factor is stress, which could plausibly lead to COPD exacerbations as it can trigger inflammation (3, 4) and is associated with increased smoking (5), which are both implicated in COPD pathology (2). Work is an important source of stress in the age groups in which COPD is typically diagnosed (1, 6). However, we are not aware of previous investigations of work-related stress and the risk of COPD exacerbations.In this study, we examined the associations between job strain (the most widely studied conceptualisation of work-related stress) and severe COPD exacerbations using individual-level data from 10 prospective cohort studies from the Individual Participant Data Meta-analysis in Working Populations (IPD-Work) Consortium (7). Job strain is defined as a combination of high demands (excessive amounts of work) and low control (having little influence on what tasks to.
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| 15. |
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| 16. |
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| 17. |
- Laukkanen, P., et al.
(författare)
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Anomalous bismuth-stabilized (2x1) reconstructions on GaAs(100) and InP(100) surfaces
- 2008
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 100, s. 086101-
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Tidskriftsartikel (refereegranskat)abstract
- First-principles phase diagrams of bismuth-stabilized GaAs- and InP(100) surfaces demonstrate for the first time the presence of anomalous (2 x 1) reconstructions, which disobey the common electron counting principle. Combining these theoretical results with our scanning-tunneling-microscopy and photoemission measurements, we identify novel (2 x 1) surface structures, which are composed of symmetric Bi-Bi and asymmetric mixed Bi-As and Bi-P dimers, and find that they are stabilized by stress relief and pseudogap formation.
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| 18. |
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| 19. |
- Punkkinen, M. P. J., et al.
(författare)
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Bismuth-stabilized (2x1) and (2x4) reconstructions on GaAs(100) surfaces : Combined first-principles, photoemission, and scanning tunneling microscopy study
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 78, s. 195304-
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Tidskriftsartikel (refereegranskat)abstract
- Bismuth adsorbate-stabilized (2x1) and (2x4) reconstructions of the GaAs(100) surfaces have been studied by first-principles calculations, valence-band and core-level photoelectron spectroscopies, and scanning tunneling microscopy. It is demonstrated that large Bi atom size leads to the formation of the pseudogap at the Fermi energy and to the lower energy of an adsorbate-derived surface band, which contributes to the stabilization of the exceptional Bi/GaAs(100)(2x1) reconstruction. It is proposed that the Bi/GaAs(100)(2x4) reconstructions include asymmetric mixed Bi-As dimers, in addition to the Bi-Bi dimers. Based on the calculations, we solve the atomic origins of the surface core-level shifts (SCLSs) of the Bi 5d photoemission spectra from the Bi/GaAs(100)(2x4) surfaces. This allows for resolving the puzzle related to the identification of two SCLS components often found in the measurements of the Bi 5d and Sb 4d core-level emissions of the Bi/III-V and Sb/III-V(100)(2x4) surfaces. Finally, the reason for the absence of the common (2x4)-beta 2 structure and additional support for the stability of the (2x1) structure on the Bi/III-V(100) surfaces are discussed in terms of Bi atom size and subsurface stress.
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| 20. |
- Punkkinen, M. P. J., et al.
(författare)
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Surface core-level shifts of GaAs(100)(2x4) from first principles
- 2007
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 76:11
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Tidskriftsartikel (refereegranskat)abstract
- First-principles calculations show that measured surface core-level shifts (SCLSs) of the GaAs(100)(2x4) surfaces can be described within the initial state effects. The calculated As 3d and Ga 3d SCLSs for the beta 2 and alpha 2 reconstructions of the GaAs(100)(2x4) surfaces are in reasonable agreement with recent measurements. In particular, the results confirm that both the lower and the higher binding energy SCLSs, relative to the bulk emission in the As 3d photoelectron spectra, are intrinsic properties of the GaAs(100)(2x4) surfaces. The most positive and most negative As shifts are attributed to the third layer As atoms, which differs from the previous intuitive suggestions. In general, calculations show that significant SCLSs arise from deep layers, and that there are more than two SCLSs. Our previously measured As 3d spectra are fitted afresh using the calculated SCLSs. The intensity ratios of the SCLSs, obtained from the fits, show that as the heating temperature of the GaAs(100)(2x4) surface is increased gradually, the area of the alpha 2 reconstruction increases on the surface, but the beta 2 phase remains within the whole temperature range, in agreement with previous experimental findings. Our results show that the combination of the experimental and theoretical results is a prerequisite for the accurate analysis of the SCLSs of the complex reconstructed surfaces.
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| 21. |
- Pääkkö, M., et al.
(författare)
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Enzymatic hydrolysis combined with mechanical shearing and high-pressure homogenization for nanoscale cellulose fibrils and strong gels
- 2007
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 8:6, s. 1934-1941
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Tidskriftsartikel (refereegranskat)abstract
- Toward exploiting the attractive mechanical properties of cellulose I nanoelements, a novel route is demonstrated, which combines enzymatic hydrolysis and mechanical shearing. Previously, an aggressive acid hydrolysis and sonication of cellulose I containing fibers was shown to lead to a network of weakly hydrogen-bonded rodlike cellulose elements typically with a low aspect ratio. On the other hand, high mechanical shearing resulted in longer and entangled nanoscale cellulose elements leading to stronger networks and gels. Nevertheless, a widespread use of the latter concept has been hindered because of lack of feasible methods of preparation, suggesting a combination of mild hydrolysis and shearing to disintegrate cellulose I containing fibers into high aspect ratio cellulose I nanoscale elements. In this work, mild enzymatic hydrolysis has been introduced and combined with mechanical shearing and a high-pressure homogenization, leading to a controlled fibrillation down to nanoscale and a network of long and highly entangled cellulose I elements. The resulting strong aqueous gels exhibit more than 5 orders of magnitude tunable storage modulus G' upon changing the concentration. Cryotransmission electron microscopy, atomic force microscopy, and cross-polarization/magic-angle spinning (CP/MAS) C-13 NMR suggest that the cellulose I structural elements obtained are dominated by two fractions, one with lateral dimension of 5-6 nm and one with lateral dimensions of about 10-20 nm. The thicker diameter regions may act as the junction zones for the networks. The resulting material will herein be referred to as MFC (microfibrillated cellulose). Dynamical rheology showed that the aqueous suspensions behaved as gels in the whole investigated concentration range 0.125-5.9% w/w, G' ranging from 1.5 Pa to 10(5) Pa. The maximum G' was high, about 2 orders of magnitude larger than typically observed for the corresponding nonentangled low aspect ratio cellulose I gels, and G' scales with concentration with the power of approximately three. The described preparation method of MFC allows control over the final properties that opens novel applications in materials science, for example, as reinforcement in composites and as templates for surface modification.
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| 24. |
- Toimela, J.S., et al.
(författare)
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Association of obesity to reaction time and visual memory in schizophrenia
- 2024
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Ingår i: Schizophrenia Research. - : Elsevier. - 2215-0013. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders.Aims: Our aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder.Methods: The study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory.Results: Obesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures.Conclusions: The results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.
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