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Sökning: WFRF:(Koskinen Seppo)

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  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
  • Björkman, Ann-Sofi, 1983-, et al. (författare)
  • Diagnostic accuracy of dual-energy CT for detection of bone marrow lesions in the subacutely injured knee with MRI as reference method
  • 2020
  • Ingår i: Acta Radiologica. - : SAGE PUBLICATIONS LTD. - 0284-1851 .- 1600-0455. ; 61:6, s. 749-759
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dual-energy computer tomography (DECT) can detect post-traumatic bone marrow lesions. Prospective studies of the knee with large numbers of participants and intra-observer agreement assessment are limited. Purpose To investigate the diagnostic accuracy of DECT in detecting bone marrow lesions as well as estimating the bone marrow lesion volume in patients with suspected anterior cruciate ligament trauma with magnetic resonance imaging (MRI) as reference standard. Material and Methods Forty-eight consecutive patients with suspected anterior cruciate ligament injury were imaged bilaterally with DECT within a mean of 25 days (range 4-55 days) following injury and MRI within seven days of DECT. Two readers analyzed DECT virtual non-calcium-blinded images. Consensus MRI was reference standard. Intra- and inter-observer agreement were determined using weighted kappa statistics. Sensitivity, specificity, and negative and positive predictive values were calculated. Bone marrow lesion volumes were measured; for comparison, intra-class correlation coefficient was used. Results The 48 patients (26 men, 22 women; mean age 23 years, age range 15-37 years) were imaged bilaterally yielding 52 knees with bone marrow lesions, of which 44 were in the femur and 41 were in the tibia. Intra- and inter-observer agreement to detect bone marrow lesions was moderate and fair to moderate (kappa 0.54-0.66, 95% confidence interval [CI] 0.39-0.80 and 0.37-0.41, 95% CI 0.20-0.57) and overall sensitivity and specificity were 70.1% and 69.1%, respectively. Positive and negative predictive values were 72.9% and 66.1%, respectively. Bone marrow lesion volumes showed excellent intra- and inter-observer agreement (0.83-0.91, 95% CI 0.74-0.94 and 0.76-0.78, 95% CI 0.57-0.87). Conclusion The diagnostic performance of DECT to detect bone marrow lesions in the subacutely injured knee was moderate with intra- and inter-observer agreement ranging from moderate to substantial and fair to moderate. Bone marrow lesion volume correlation was excellent.
  • Danaei, Goodarz, et al. (författare)
  • Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
  • 2015
  • Ingår i: The Lancet Diabetes & Endocrinology. - : Elsevier. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
  • Dupuis, Josee, et al. (författare)
  • New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
  • 2010
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 42:2, s. 32-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
  • Evangelou, Evangelos, et al. (författare)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
  • Guido, Davide, et al. (författare)
  • Pain rates in general population for the period 1991-2015 and 10-years prediction : results from a multi-continent age-period-cohort analysis
  • 2020
  • Ingår i: Journal of Headache and Pain. - 1129-2369 .- 1129-2377. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. Methods We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content self-reported pain experienced at the time of the interview, with a dichotomous (yes or no) modality. Results Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. Conclusions Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
  • 2010
  • Ingår i: Nature genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 42:11, s. 949-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10(-9) to P = 1.8 × 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10(-3) to P = 1.2 × 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
  • Lango Allen, Hana, et al. (författare)
  • Hundreds of variants clustered in genomic loci and biological pathways affect human height.
  • 2010
  • Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
  • Lu, Yingchang, et al. (författare)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.
  • 2016
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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