| 1. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 2. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 3. |
- Daly, Robin M., et al.
(författare)
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Association Between Changes in Habitual Physical Activity and Changes in Bone Density, Muscle Strength, and Functional Performance in Elderly Men and Women
- 2008
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 56:12, s. 2252-2260
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the long-term effects of habitual physical activity on changes in musculoskeletal health, functional performance, and fracture risk in elderly men and women. Ten-year prospective population-based study. Malmo-Sjobo Prospective Study, Sweden. Participants were 152 men and 206 women aged 50, 60, 70, and 80 who were followed for 10 years. Distal radius bone mineral density (BMD) (single photon absorptiometry), upper limb muscle (grip) strength, balance, gait velocity, occupational and leisure-time activity, and fractures (interview-administered questionnaire) were reassessed after 10 years. Annual changes for all measures were compared between participants with varying habitual physical activity histories at baseline and follow-up: inactive-inactive (n=202), active-inactive (n=47), inactive-active (n=49), and active-active (n=60). Data for men and women were pooled, because there were no sex-by-activity group interactions. To detect possible differences in fracture incidence between the varying habitual activity groups, participants were classified into two activity groups based on their activity classification at baseline and follow-up: inactive:less active versus active:more active. The annual rate of bone loss was 0.6% per year less in individuals classified as active at both time points than in those classified as inactive at both time points (P <.01). Similar results were observed for balance, but there was no effect of varying habitual activity on changes in muscle strength or gait velocity. There were also no differences in fracture incidence between individuals categorized as active:more active and those categorized as inactive:less active during the follow-up (adjusted hazard ratio=0.90, 95% confidence interval (CI)=0.42-1.90). This study showed that elderly men and women who maintained a habitually active lifestyle over 10 years had lower bone loss and retained better balance than those who remained habitually inactive.
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| 4. |
- Daly, Robin M., et al.
(författare)
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Gender specific age-related changes in bone density, muscle strength and functional performance in the elderly: a-10 year prospective population-based study
- 2013
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Age-related losses in bone mineral density (BMD), muscle strength, balance, and gait have been linked to an increased risk of falls, fractures and disability, but few prospective studies have compared the timing, rate and pattern of changes in each of these measures in middle-aged and older men and women. This is important so that targeted strategies can be developed to optimise specific musculoskeletal and functional performance measures in older adults. Thus, the aim of this 10-year prospective study was to: 1) characterize and compare age-and gender-specific changes in BMD, grip strength, balance and gait in adults aged 50 years and over, and 2) compare the relative rates of changes between each of these musculoskeletal and functional parameters with ageing. Methods: Men (n = 152) and women (n = 206) aged 50, 60, 70 and 80 years recruited for a population-based study had forearm BMD, grip strength, balance and gait velocity re-assessed after 10-years. Results: The annual loss in BMD was 0.5-0.7% greater in women compared to men aged 60 years and older (p < 0.05- < 0.001), but there were no gender differences in the rate of loss in grip strength, balance or gait. From the age of 50 years there was a consistent pattern of loss in grip strength, while the greatest deterioration in balance and gait occurred from 60 and 70 years onwards, respectively. Comparison of the changes between the different measures revealed that the annual loss in grip strength in men and women aged < 70 years was 1-3% greater than the decline in BMD, balance and gait velocity. Conclusion: There were no gender differences in the timing (age) and rate (magnitude) of decline in grip strength, balance or gait in Swedish adults aged 50 years and older, but forearm BMD decreased at a greater rate in women than in men. Furthermore, there was heterogeneity in the rate of loss between the different musculoskeletal and function parameters, especially prior to the age of 70 years, with grip strength deteriorating at a greater rate than BMD, balance and gait.
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| 5. |
- Fritz, Jesper, et al.
(författare)
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Influence of a School-based Physical Activity Intervention on Cortical Bone Mass Distribution : A 7-year Intervention Study
- 2016
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 99:5, s. 443-453
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Tidskriftsartikel (refereegranskat)abstract
- Cortical bone mass and density varies across a bones length and cross section, and may be influenced by physical activity. This study evaluated the long-term effects of a pediatric school-based physical activity intervention on tibial cortical bone mass distribution. A total of 170 children (72 girls and 98 boys) from one school were provided with 200 min of physical education per week. Three other schools (44 girls and 47 boys) continued with the standard 60 min per week. Tibial total and cortical area, cortical density, polar stress–strain index (SSI), and the mass and density distribution around the center of mass (polar distribution, mg) and through the bones cortex (radial distribution subdivided into endo-, mid-, and pericortical volumetric BMD: mg/cm3) at three sites (14, 38, and 66 %) were assessed using peripheral quantitative computed tomography after 7 years. Girls in the intervention group had 2.5 % greater cortical thickness and 6.9 % greater SSI at the 66 % tibia, which was accompanied by significantly greater pericortical volumetric BMD compared to controls (all P <0.05). Region-specific differences in cortical mass were also detected in the anterior, medial, and lateral sectors at the 38 and 66 % tibial sites. There were no group differences at the 14 % tibia site in girls, and no group differences in any of the bone parameters in boys. Additional school-based physical education over seven years was associated with greater tibial structure, strength, and region-specific adaptations in cortical bone mass and density distribution in girls, but not in boys.
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| 6. |
- Kiss, Nicole, et al.
(författare)
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Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss.
- 2020
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Ingår i: Current osteoporosis reports. - : Springer Science and Business Media LLC. - 1544-2241 .- 1544-1873. ; 18:3, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The aim of this narrative review is to summarise recent literature on the effects of exercise and nutrition interventions alone or in combination on muscle and bone loss in people with cancer.RECENT FINDINGS: There is emerging evidence to support the inclusion of targeted exercise and nutrition strategies to counter loss of muscle and bone associated with cancer treatments. Although research in this field is advancing, the optimal exercise and nutrition prescription to combat cancer-related bone and muscle loss remain unknown. This review identifies specific components of nutrition and exercise interventions that are promising although require further exploration through studies designed to determine the effect on muscle and bone. A focused research effort is required to elucidate the full potential of exercise and nutrition intervention for people with cancer at risk of bone and muscle loss.
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| 7. |
- Löfgren, Bjarne, et al.
(författare)
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An Increase in School-Based Physical Education Increases Muscle Strength in Children.
- 2013
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Ingår i: Medicine & Science in Sports & Exercise. - 1530-0315. ; 45:5, s. 997-1003
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Children and adolescents are encouraged to maintain a habitually active lifestyle because of the known health benefits associated with regular physical activity, but there are some reports that a high level of activity may be associated with increased fracture risk. This prospective controlled exercise intervention study in pre-pubertal children evaluated if a school-based exercise intervention could enhance growth related gains in muscle strength and muscular function without affecting fracture risk. METHODS: Fractures were registered in 417 girls and 500 boys aged 7-9 years in the intervention and in 836 age-matched girls and 872 boys. The intervention included 40 minutes/day of school physical education for two years whereas the controls achieved 60 minutes/week. In a subsample consisting of 49 girls and 80 boys in the intervention and 50 girls and 53 boys in the control group, body composition was measured by dual X-ray absorptiometry (DXA), muscle strength by isokinetic Peak Torque (PT) of the knee extensors and flexors at 60 and 180 °/seconds by a computerized dynamometer and neuromuscular performance by Vertical Jump Height (VJH). RESULTS: The rate ratio [RR (95% confidence interval)] for children in the intervention group to sustain a fracture was 1.07 (0.66, 1.68). The annual gain in knee extensor PT at 180°/seconds was significantly higher for both girls (p<0.001) and boys (p<0.01) in the intervention compared to the control group. Boys in the intervention group also had a greater annual gain in knee flexion PT at 180 °/seconds (p<0.001) and girls a greater gain in VJH (p<0.05). CONCLUSIONS: An increase in school-based physical education from 60 to 200 min/week enhanced muscle strength in pre-pubertal children without affecting fracture risk.
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| 8. |
- Löwemark, Ludvig, et al.
(författare)
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Practical guidelines and recent advances in the Itrax XRF core-scanning procedure
- 2019
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Ingår i: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 514, s. 16-29
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Tidskriftsartikel (refereegranskat)abstract
- XRF core scanning has evolved to become a standard analytical technique for the rapid assessment of elemental, density and textural variations in a wide range of sediments and other materials, with applications ranging from palaeoceanography, paleoclimatology, geology, and environmental forensics to environmental protection. In general, scanning provides rapid, non-destructive acquisition of elemental and textural variations at sub-millimetre resolution for a wide range of materials. Numerous procedural adaptations have been developed for the growing number of applications, such as analyses of unconsolidated, water-rich sediments, powdered soil samples, or resin bags. Here, practical expertise and guidance from the Itrax community, gained over 15 years, is presented that should provide insights for new and experienced users.
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| 9. |
- Rioux, John D., et al.
(författare)
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Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease
- 2001
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 29:2, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease1. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10−4). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P<2×10−7) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence—each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.
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| 10. |
- Rosengren, Björn, et al.
(författare)
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Bone mineral density and incidence of hip fracture in Swedish urban and rural women 1987-2002.
- 2010
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; Jul 1, s. 453-459
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Although the incidence of hip fracture during the past 50 years has increased, a break in this trend has been reported in the last decade. Whether this change is attributable to changes in bone mineral density (BMD) or whether it varies between urban and rural regions is unknown. Methods We evaluated changes in annual hip fracture incidence in women aged >/= 50 years in one urban population (n = 51,757) and one rural population (n = 26,446) from 1987 to 2002. We also examined secular differences in BMD (mg/cm(2)), evaluated by single-photon absorptiometry at the distal radius, prevalence of osteoporosis, and several other risk factors for hip fracture in one population-based sample of urban women and one sample of rural women aged 50-80 years at two time points: 1988/89 (n = 257 and n = 180, respectively) and 1998/99 (n = 171 and n = 118, respectively). Results No statistically significant changes were evident in annual age-adjusted hip fracture incidence per 10(4) when analyzing all women (-0.01 per year (95% CI: -0.37, 0.35)), rural women (-0.38 per year (-1.05, 0.28)), or urban women (0.19 per year (-0.28, 0.67)). BMD (expressed as T-score) was similar in 1988/99 and 1998/99 when analyzing all women (-0.09 (-0.26, 0.09)), urban women (-0.04 (-0.27, 0.19)), or rural women (-0.15 (-0.42, 0.13)) women. Interpretation Since no changes in age-adjusted hip fracture incidence and no differences in BMD were found during the study period, changes evident in the other risk factors for hip fracture that we investigated (such as gait velocity and balance) are either of minor importance or are counteracted by changes in other risk factors.
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