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1.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution
  • 2015
  • Ingår i: Nature. - 0028-0836. ; 518:7538, s. 187-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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2.
  • Abdallah, J., et al. (författare)
  • Study of double-tagged gamma gamma events at LEPII
  • 2006
  • Ingår i: European physical journal C. - Springer. - 1434-6044. ; 46:3, s. 559-568
  • Tidskriftsartikel (refereegranskat)abstract
    • Double-tagged interactions of photons with virtualities Q(2) between 10 GeV2 and 200 GeV2 are studied with the data collected by DELPHI at LEPII from 1998 to 2000, corresponding to an integrated luminosity of 550 pb(-1). The gamma*gamma* -> mu(+)mu(-) data agree with QED predictions. The cross-section of the reaction gamma*gamma* -> hadrons is measured and compared to the LO and NLO BFKL calculations.
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3.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
4.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036. ; 45:11, s. 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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5.
  • 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
  • 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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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. ; 518:7538, s. 197-206
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 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 ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in 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.
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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 Science. - 1553-7390. ; 9:6, s. e1003500
  • 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<5×10(-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.
  • Abdallah et al., DELPHI Collaboration: J, et al. (författare)
  • A measurement of the tau hadronic branching ratios
  • 2006
  • Ingår i: European Physical Journal C. - 1434-6044. ; 46:1, s. 1-26
  • Tidskriftsartikel (refereegranskat)abstract
    • The exclusive and semi-exclusive branching ratios of the tau lepton hadronic decay modes (h(-)upsilon(tau), h(-)pi(0)upsilon(tau), h(-)pi(0)pi(0)upsilon(tau), h(-) >= 2 pi(0)nu(tau), 2h(-)h(+)upsilon(tau), 2h(-)h(+)>= 2 pi(0)upsilon(tau), 3h(-)2h(+)upsilon(tau) and 3h(-)2h(+) >= 1 pi(0)upsilon(tau)) were measured with data from the DELPHI detector at LEP.
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9.
  • Abdallah et al., DELPHI Collaboration: J, et al. (författare)
  • Investigation of colour reconnection in WW events with the DELPHI detector at LEP-2
  • 2007
  • Ingår i: European Physical Journal C. - EDP Sciences. - 1434-6044. ; 51:2, s. 249-269
  • Tidskriftsartikel (refereegranskat)abstract
    • In the reaction e(+)e(-) -> WW -> (q(1) (q) over bar (2))(q(3)(q) over bar (4)) the usual hadronization models treat the colour singlets q(1)(q) over bar (2) and q(3)(q) over bar (4) coming from two W bosons independently. However, since the. nal state partons may coexist in space and time, cross-talk between the two evolving hadronic systems may be possible during fragmentation through soft gluon exchange. This e. ect is known as colour reconnection. In this article the results of the investigation of colour reconnection e. ects in fully hadronic decays of W pairs in DELPHI at LEP are presented. Two complementary analyses were performed, studying the particle. ow between jets and W mass estimators, with negligible correlation between them, and the results were combined and compared to models. In the framework of the SK-I model, the value for its. parameter most compatible with the data was found to be: (SK)-S-kappa-I = 2.2(-1.3) (+2.5) corresponding to the probability of reconnection P-reco to be in the range 0.31 < P-reco < 0.68 at 68% confidence level with its best value at 0.52.
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10.
  • Abdallah et al., DELPHI Collaboration: J, et al. (författare)
  • Single intermediate vector boson production in e(+)e(-) collisions at root s=183-209 GeV
  • 2006
  • Ingår i: European physical journal C. - Springer. - 1434-6044. ; 45:2, s. 273-289
  • Tidskriftsartikel (refereegranskat)abstract
    • The production of single charged and neutral intermediate vector bosons in e(+)e(-) collisions has been studied in the data collected by the DELPHI experiment at LEP at centre-of-mass energies between 183 and 209 GeV, corresponding to an integrated luminosity of about 640 pb(-1). The measured cross-sections for the reactions, determined in limited kinematic regions, are in agreement with the Standard Model predictions.
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