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Sökning: WFRF:(Elmstahl S.)

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1.
  • Chen, Ji, et al. (författare)
  • The trans-ancestral genomic architecture of glycemic traits
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:6, s. 840-860
  • Tidskriftsartikel (refereegranskat)abstract
    • Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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2.
  • Cornelis, M. C., et al. (författare)
  • Targeted proteomic analysis of habitual coffee consumption
  • 2018
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 283:2, s. 200-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health. Objective: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418). Methods: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay. Results: Four protein–coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10−3): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, −0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, −0.025 SD per time of coffee, P = 0.004). The negative coffee–CHI3L association replicated in EpiHealth (β, −0.07, P = 1.15 × 10−7), but not in ULSAM (β, −0.034, P = 0.16). Conclusions: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee–CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.
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3.
  • Folkersen, Lasse, et al. (författare)
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
  • 2020
  • Ingår i: Nature metabolism. - : Springer Nature. - 2522-5812. ; 2:10, s. 1135-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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4.
  • Figarska, Sylwia M., et al. (författare)
  • Associations of Circulating Protein Levels With Lipid Fractions in the General Population
  • 2018
  • Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - : Lippincott Williams & Wilkins. - 1524-4636 .- 1079-5642. ; 38:10, s. 2505-2518
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective- Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. Approach and Results- We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels. Conclusions- Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.
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5.
  • Frisendahl, Nathalie, et al. (författare)
  • Predictive Performance of the FIF Screening Tool in 2 Cohorts of Community-Living Older Adults
  • 2020
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 21:12, s. 1900-1905
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The First-time Injurious Fall (FIF) screening tool was created to identify fall risk in communityliving older adults who may benefit from primary preventive interventions. The aim of this study was to evaluate the predictive performance of the FIF tool in 2 cohorts of older adults. Design: Longitudinal cohort study. Setting and Participants: The Swedish National Study on Aging and Care in Skane (SNAC-S) and Blekinge (SNAC-B), Sweden. Community-living people aged >= 60 years (n = 2766). Methods: Nurses and physicians collected data in the 2 cohorts through interviews and testing. Data on injurious falls were collected from register data and were defined as receipt of care after a fall. The FIF tool, consisting of 3 questions and 1 balance test, was examined in relation to injurious falls for up to 5 years of follow-up using Cox proportional hazards models. The predictive performance of the FIF tool was further explored using Harrell C statistic and Youden cut-off for sensitivity and specificity. Results: The hazard ratios (HRs) of an injurious fall in the high-risk group for women and men were 3.80 (95% confidence interval [CI] 2.53, 5.73) and 5.10 (95% CI 2.57, 10.12) in SNAC-S and 4.45 (95% CI 1.86, 10.61) and 32.58 (95% CI 4.30, 247.05) in SNAC-B compared with those in the low risk group. The sensitivity and specificity of the Youden cut-off point (3 or higher for high-risk) were 0.64 and 0.69 for women and 0.68 and 0.69 for men in SNAC-S, and 0.64 and 0.74 for women and 0.94 and 0.68 for men in SNAC-B. The predictive values (Harrell C statistic) for the scores for women and men were 0.73 and 0.74 in SNAC-S and 0.72 and 0.89 in SNAC-B. Conclusions and Implications: Our results suggest that the FIF tool is a valid tool to use for prediction of first-time injurious falls in community-living older adults. (C) 2020 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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6.
  • Wimo, Anders, et al. (författare)
  • Formal and informal care of community-living older people : a population-based study from the Swedish National study on Aging and Care
  • 2017
  • Ingår i: The Journal of Nutrition, Health & Aging. - : Springer. - 1279-7707 .- 1760-4788. ; 21:1, s. 17-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Study formal and informal care of community-living older people in the Swedish National study of Aging and Care (SNAC).Design: Cross-sectional, population based cohort.Setting: Three areas in Sweden: Municipality of Nordanstig, Stockholm and Skåne County.Participants: 3,338 persons ≥72 years.Measurements: Patterns and amounts of informal and formal care by cognition and area of residence.Results: 73% received no care; 14% formal care; and 17% informal care (7% received both). In the whole study population, including those who used no care, individuals in small municipalities received 9.6 hours of informal care/month; in mid-size municipalities, 6.6; and in urban areas, 5.6. Users of informal care received 33.1 hours of informal care/month in small municipalities, 54.6 in mid-size municipalities and 36.1 in urban areas. Individuals with cognitive impairment received 14.1 hours of informal care/month, 2.7 times more than people with no/slight impairment. In the whole study population, individuals in small municipalities received an average of 3.2 hours of formal care/month; in mid-size municipalities 1.4; and in urban areas, 2.6. Corresponding figures for formal care users were 29.4 hours in small municipalities, 13.6 in mid-size municipalities and 16.7 in urban areas. Formal care users received 7.1 hours, and informal care users, 5.9 hours for each hour/month received by people in the study population as a whole.Conclusions: More informal than formal care was provided. Informal care is more frequent in small municipalities than urban areas and for those with than without cognitive impairment. The relationship between data on the whole population and the data on users or care indicates that population-based data are needed to avoid overestimates of care.
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7.
  • Beijer, Kristina, et al. (författare)
  • Interaction between physical activity and television time on blood pressure level : Cross-sectional data from 45 000 individuals
  • 2018
  • Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 36:5, s. 1041-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect. Methods: Linear regression analysis on cross-sectional data was performed in more than 45 000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time. Results: High physical activity was associated with lower DBP (P = 0.001), but not SBP. Active middle-aged men had lower DBP (-1.1 mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P < 0.001) and DBP (P = 0.011) in both sexes and in most age groups. Watching 3 h instead of 1 h television per day was associated with higher SBP in middle-aged women (SBP: 1.1 mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2 mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3 h per day) in terms of DBP. Conclusion: Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.
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8.
  • Elmstahl, S., et al. (författare)
  • Body composition in patients with Alzheimer's disease and healthy controls
  • 1992
  • Ingår i: Journal of Clinical and Experimental Gerontology. - 0192-1193. ; 14:1, s. 17-31
  • Tidskriftsartikel (refereegranskat)abstract
    • In Alzheimer's disease (AD), decreased physical activity and nutritional problems are parts of the natural course with probable implications on body composition. Body fat and lean body mass were measured with a bioelectrical impedance method in 25 women who had AD according to the criteria of NINCDS- ADRDA and in 63 health age-matched controls. The patients with AD had 9.5 kg lower body weight (p<0.01), due to almost 4.0 kg lower body fat and 6.0 kg lower lean body mass (p<0.001). This might imply a higher risk for morbidity and mortality. Body weight and lean body mass decreased with age in AD patients but not in the healthy control women. In the control group, the unmarried women had more than 13 kg lower body weight and 9 kg lower body fat than the mean values of all other marital status groups (p<0.01). The maintenance of lean body mass in the very healthy old indicate the possibilities for physical activity.
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9.
  • Lagergren, Mårten, et al. (författare)
  • Horizontal and vertical targeting : a population-based comparison of public eldercare services in urban and rural areas of Sweden
  • 2016
  • Ingår i: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 28:1, s. 147-158
  • Tidskriftsartikel (refereegranskat)abstract
    • The concepts of target efficiency can be used to assess the extent to which service provision is in line with the needs of the population. Horizontal target efficiency denotes the extent to which those deemed to need a service receive it and vertical target efficiency is the corresponding extent to which those who receive services actually need them. The aim of this study was to assess the target efficiency of the Swedish eldercare system and to establish whether target efficiencies differ in different geographical areas such as large urban, midsize urban and rural areas. Vertical efficiency was measured by studying those people who received eldercare services and was expressed as a percentage of those who received services who were functionally dependent. To measure horizontal target efficiency, data collected at baseline in the longitudinal population study SNAC (Swedish National study on Aging and Care) during the years 2001-2004 were used. The horizontal efficiency was calculated as the percentage of functionally dependent persons who received services. Functional dependency was measured as having difficulty with instrumental activities of daily living (IADL) and/or personal activities of daily living (PADL). Services included long-term municipal eldercare services (LTC). Horizontal target efficiency for the public LTC system was reasonably high in all three geographical areas, when using dependency in PADL as the measure of need (70-90 %), but efficiency was lower when the less restrictive measure of IADL dependency was used (40-50 %). In both cases, the target efficiency was markedly higher in the large urban and the rural areas than in the midsize urban areas. Vertical target efficiency showed the same pattern-it was almost 100 % in all areas for IADL dependency, but only 50-60 % for PADL dependency. Household composition differed in the areas studied as did the way public long-term care was provided to people living alone as compared to those co-habiting.
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10.
  • Lind, Lars, et al. (författare)
  • Change in Body Weight from Age 20 Years Is a Powerful Determinant of the Metabolic Syndrome
  • 2017
  • Ingår i: Metabolic syndrome and related disorders. - : Mary Ann Liebert, Inc.. - 1557-8518 .- 1540-4196. ; 15:3, s. 112-117
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Higher body weight is a well-known determinant of the metabolic syndrome (MetS) and its components. It is however less well studied how the change in weight from age 20 years to middle age or old age affects MetS development.METHODS: In the community-based EpiHealth (n = 19,000, age range 45 to 75 years, 56% females) and PIVUS (n = 1000, all aged 70 years, 50% females) studies, the participants were asked about their body weight at age 20 years. Data were collected to determine MetS prevalence (NCEP ATP III criteria).RESULTS: In EpiHealth, the probability of having MetS increased fairly linearly with increasing weight from age 20 in the obese [odds ratios (OR) 1.04 per kg change in weight, 95% confidence interval (CI) 1.03-1.05, P < 0.0001], as well as in the overweight (OR 1.15, 95% CI 1.14-1.17, P < 0.0001) and normal-weight (OR 1.18, 95% CI 1.14-1.21, P < 0.0001), subjects after adjustment for age, sex, body mass index (BMI) at age 20, alcohol intake, smoking, education, and exercise habits. Also in the PIVUS study, the change in weight over 50 years was related to prevalent MetS (OR 1.08 per kg change in weight, 95% CI 1.06-1.10, P < 0.0001). In both studies, self-reported BMI at age 20 was related to prevalent MetS.CONCLUSION: Self-reported weight gain from age 20 was strongly and independently associated with prevalent MetS both in middle age or old age. Interestingly, this relationship was not restricted only to obese subjects. Our data provide additional support for the importance of maintaining a stable weight throughout life.
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