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Sökning: WFRF:(Johansson Asa)

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  • [1]234567...8Nästa
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1.
  • Deloukas, Panos, et al. (författare)
  • Large-scale association analysis identifies new risk loci for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
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2.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:11, s. 1345-1345
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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3.
  • Harnek, Jan, et al. (författare)
  • The 2011 outcome from the Swedish Health Care Registry on Heart Disease (SWEDEHEART).
  • 2013
  • Ingår i: Scandinavian Cardiovascular Journal. - Taylor & Francis. - 1651-2006. ; 47, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objectives. The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) collects data to support the improvement of care for heart disease. Design. SWEDEHEART collects on-line data from consecutive patients treated at any coronary care unit n = (74), followed for secondary prevention, undergoing any coronary angiography, percutaneous coronary intervention, percutaneous valve or cardiac surgery. The registry is governed by an independent steering committee, the software is developed by Uppsala Clinical Research Center and it is funded by The Swedish national health care provider independent of industry support. Approximately 80,000 patients per year enter the database which consists of more than 3 million patients. Results. Base-line, procedural, complications and discharge data consists of several hundred variables. The data quality is secured by monitoring. Outcomes are validated by linkage to other registries such as the National Cause of Death Register, the National Patient Registry, and the National Registry of Drug prescriptions. Thanks to the unique social security number provided to all citizens follow-up is complete. The 2011 outcomes with special emphasis on patients more than 80 years of age are presented. Conclusion. SWEDEHEART is a unique complete national registry for heart disease.
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4.
  • 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. - 1546-1718. ; 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 x 10(-9) to P = 1.8 x 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 x 10(-3) to P = 1.2 x 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.
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5.
  • Lazarevic, Vladimir, et al. (författare)
  • Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia.
  • 2015
  • Ingår i: European Journal of Haematology. - Wiley-Blackwell. - 1600-0609. ; 94:5, s. 419-423
  • Tidskriftsartikel (refereegranskat)abstract
    • Unsuccessful cytogenetics (UC) in acute myeloid leukaemia (AML) patients treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. In order to ascertain whether this holds true also in unselected AML patients, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below the age of 80 years without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high risk (HR) AML, intermediate risk (IR), and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR, and HR AML patients without UC and UPC were 64%, 31%, and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis. This article is protected by copyright. All rights reserved.
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6.
  • Locke, Adam E., et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-U401
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P &lt; 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for &gt;20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p>
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7.
  • Randall, Joshua C., et al. (författare)
  • Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
  • 2013
  • Ingår i: PLoS Genetics. - Public Library of Science. - 1553-7404. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5x10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
8.
  • Svedberg, Petra, et al. (författare)
  • Psychometric evaluation of 'The 25-item Sex after MI Knowledge Test' in a Swedish context.
  • 2012
  • Ingår i: Scandinavian Journal of Caring Sciences. - Wiley-Blackwell. - 1471-6712. ; 26, s. 203-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychometric evaluation of 'The 25-item Sex after MI Knowledge Test' in a Swedish context The patients' sexual life after a myocardial infarction is important for his/her quality of life. In spite of this, many patients are in doubt regarding their sex life after a myocardial infarction (MI) and the sexual information received, and counselling from health care providers has been seen to be insufficient. The purpose of this study was to evaluate the psychometric properties of 'The 25-item Sex after MI Knowledge Test' in a Swedish context. A convenience sample was recruited. The scale was translated into Swedish and completed by 79 former patients from The Heart and Lung Patients' National Association on two occasions, with an interval of 2 weeks. The scale was tested for face and content validity, internal consistency and test-retest reliability. The result in this study indicates that the instrument has good face and content validity and displayed a moderate internal consistency (alpha 0.61). The instrument showed some level of instability in test-retest reliability with 60% of the items presenting moderate or strong agreement between the test and retest. Further studies that use this instrument in larger and more diverse samples are thus needed.
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9.
  • Tedgren, Asa Carlsson, et al. (författare)
  • Experience from long-term monitoring of RAKR ratios in Ir-192 brachytherapy
  • 2008
  • Ingår i: Radiotherapy and Oncology. - Elsevier. - 1879-0887. ; 89:2, s. 217-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Ratios of values of brachytherapy source strengths, as measured by hospitals and vendors, comprise constant differences as, e.g., systematic errors in ion chamber calibration factors and measurement setup. Such ratios therefore have the potential to reveal the systematic changes in routines or calibration services at either the hospital or the vendor laboratory, which could otherwise be hidden by the uncertainty in the source strength values. Methods: The RAKR of each new source in 13 afterloading units at five hospitals were measured by well-type ion chambers and compared to values for the same source stated on vendor certificates. Results: Differences from unity in the ratios of RAKR values determined by hospitals and vendors are most often small and stable around their mean values to within +/- 11.5%. Larger deviations are rare but occur. A decreasing ratio, seen at two hospitals for the same source, was useful in detecting an erroneous pressure gauge at the vendor's site. Conclusions: Establishing a mean ratio of RAKR values, as measured at the hospital and supplied on the vendor certificate, and monitoring this as a function of time are an easy way for the early detection of problems with equipment or routines at either the hospital or the vendor site. (c) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 89 (2008) 217-221.
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10.
  • Teslovich, Tanya M., et al. (författare)
  • Biological, clinical and population relevance of 95 loci for blood lipids
  • 2010
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836. ; 466:7307, s. 707-713
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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