| 1. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
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| 3. |
- Kurki, MI, et al.
(författare)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 4. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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| 5. |
- Saarikangas, J, et al.
(författare)
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Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia
- 2011
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 124:8Pt 8, s. 1245-1255
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Tidskriftsartikel (refereegranskat)abstract
- MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
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| 6. |
- Kalinen, Sofia, et al.
(författare)
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Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.
- 2024
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Ingår i: European urology open science. - 2666-1683. ; 62, s. 140-150
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Tidskriftsartikel (refereegranskat)abstract
- Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.Characterization of the gut microbiota and its functions associated with PCa.In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.
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| 7. |
- Berthelsen, Hanne, et al.
(författare)
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Copenhagen Psychosocial Questionnaire : A validation study using the Job Demand-Resources model
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study aims at investigating the nomological validity of the Copenhagen Psychosocial Questionnaire (COPSOQ II) by using an extension of the Job Demands-Resources (JD-R) model with aspects of work ability as outcome. Material and methods: The study design is cross-sectional. All staff working at public dental organizations in four regions of Sweden were invited to complete an electronic questionnaire (75% response rate, n = 1345). The questionnaire was based on COPSOQ II scales, the Utrecht Work Engagement scale, and the one-item Work Ability Score in combination with a proprietary item. The data was analysed by Structural Equation Modelling. Results: This study contributed to the literature by showing that: A) The scale characteristics were satisfactory and the COPSOQ instrument could be integrated in the JD-R framework; B) Job resources arising from leadership may be a driver of the two processes included in the JD-R model; and C) Both the health impairment and motivational processes were associated with WA, and the results suggested that leadership may impact WA, in particularly by securing task resources. Conclusion: In conclusion, the nomological validity of COPSOQ was supported as the JD-R model can be operationalized by the instrument. This may be helpful for transferral of complex survey results and work life theories to practitioners in the field.
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| 8. |
- Berthelsen, Hanne, et al.
(författare)
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It is not just about occupation, but also about where you work
- 2017
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Ingår i: Community Dentistry and Oral Epidemiology. - : John Wiley & Sons. - 0301-5661 .- 1600-0528. ; 45:4, s. 372-379
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Dentistry is characterized by a meaningful but also stressful psychosocial working environment. Job satisfaction varies among staff working under different organizational forms. The aim of this study was to identify (i) to what extent crucial psychosocial work environment characteristics differ among occupations in general public dental clinics in Sweden, and (ii) how much of the variation within each occupation is attributable to the organizational level. Methods: All staff (N=1782) employed in four public dental organizations received an email with personal log-in to an electronic questionnaire based on the Copenhagen Psychosocial Questionnaire. After two reminders, a response rate of 75% was obtained. Responses from 880 nonmanagerial dentists, dental hygienists and dental nurses working in general practices were included in our analyses. Results: First, we compared the three dental occupations. We found that job demands, task resources (eg influence, possibilities for development and role clarity), strain symptoms and attitudes to work differed among occupations, dentists having the least favourable situation. Next, we compared the four organizations for each occupational group, separately. For dentists, a significant and relevant amount of variance (P<.05 and ICC >.05) was explained by the organizational level for 15 of 26 subscales, least pronounced for task resources. By contrast, for dental nurses and hygienists, the corresponding number was 2 subscales of 26. The psychosocial working environment of people working at the organization with the highest levels of strain indicators and the least positive work-related attitudes differed systematically from the organization with the most favourable profile, in particular regarding job demands and leadership aspects. Conclusion: In conclusion, the psychosocial working environment depended to a large degree on occupation and, for dentists in particular, also on their organizational affiliation. The findings suggest a potential for designing interventions at organizational level for improvements of the psychosocial working environment for dentists.
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| 9. |
- Bianchi, R, et al.
(författare)
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Is Burnout a Depressive Condition? A 14-Sample Meta-Analytic and Bifactor Analytic Study
- 2021
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Ingår i: CLINICAL PSYCHOLOGICAL SCIENCE. - : SAGE Publications. - 2167-7026 .- 2167-7034. ; 9:4, s. 579-597
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is no consensus on whether burnout constitutes a depressive condition or an original entity requiring specific medical and legal recognition. In this study, we examined burnout–depression overlap using 14 samples of individuals from various countries and occupational domains ( N = 12,417). Meta-analytically pooled disattenuated correlations indicated (a) that exhaustion—burnout’s core—is more closely associated with depressive symptoms than with the other putative dimensions of burnout (detachment and efficacy) and (b) that the exhaustion–depression association is problematically strong from a discriminant validity standpoint ( r = .80). The overlap of burnout’s core dimension with depression was further illuminated in 14 exploratory structural equation modeling bifactor analyses. Given their consistency across countries, languages, occupations, measures, and methods, our results offer a solid base of evidence in support of the view that burnout problematically overlaps with depression. We conclude by outlining avenues of research that depart from the use of the burnout construct.
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| 10. |
- Geisler, Martin, et al.
(författare)
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No job demand is an island : interaction effects between emotional demands and other types of job demands
- 2019
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Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 10, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Emotional demands are an inevitable feature of human services, and suggested to be a defining antecedent for workers’ stress and ill health. However, previous research indicate that emotional demands can have a favorably association to certain facets of human service workers’ motivation and well-being. Furthermore, recent research report that the effect of emotional demands on workers’ health and well-being seem to be contingent on the parallel level of other job demands. Still, initial investigations of interaction effects between emotional demands and other types of job demands have primarily focused on negative outcomes in terms of stress-related concerns and absenteeism. The present study investigated interaction effects between emotional demands and other types of job demands in relation to positive outcomes. In a larger sample of human service workers (social workers, n = 725), interaction effects were investigated between emotional demands and other job demands (quantitative demands, work pressure, and role conflict) for meaning in work and quality of work. Hypotheses stated that other job demands would moderate the relationship between emotional demands and positive outcomes, so that emotional demands would have a positive relation (i.e., act as a challenge) when the level of other demands is lower, but have a negative relation (i.e., act as a hindrance) when the level of other demands is high. Overall, the results provided support for the idea that emotional demands may act as a challenge. We found small but significant interaction effects between emotional demands and work pressure – in relation to meaning of work, as well as between emotional demands and quantitative demands, work pressure, and roleconflict, respectively – in relation to quality of work. Yet, the results did not support the assumption that emotional demands act as a hindrance when the level of other types of job demands is high. In sum, the results contribute by showing that emotional demands may promote human-service workers’ job attitudes when the level of parallel job demands is lower. We discuss the contribution of the study and the potential practical implications of the results, and give some suggestions for future research.
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