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Träfflista för sökning "WFRF:(Doering Angela) "

Sökning: WFRF:(Doering Angela)

  • Resultat 1-10 av 26
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1.
  • Tidskriftsartikel (refereegranskat)
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2.
  • Tidskriftsartikel (refereegranskat)
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3.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
  • 2011
  • Ingår i: Nature genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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4.
  • Lindgren, Cecilia M., et al. (författare)
  • Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution
  • 2010
  • Ingår i: PLoS Genetics. - : Public Library of Science. - 1553-7404. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P=8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.66x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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5.
  • Schunkert, Heribert, et al. (författare)
  • Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718. ; 43:4, s. 153-333
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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6.
  • 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 .- 1476-4687. ; 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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7.
  • Tidskriftsartikel (refereegranskat)
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8.
  • Tidskriftsartikel (refereegranskat)
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9.
  • Bidlingmaier, Martin, et al. (författare)
  • Reference Intervals for Insulin-like Growth Factor-1 (IGF-1) From Birth to Senescence: Results From a Multicenter Study Using a New Automated Chemiluminescence IGF-1 Immunoassay Conforming to Recent International Recommendations.
  • 2014
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 99:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Measurement of IGF-1 is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-1 assays and for establishment of normative data. Objectives: Our objectives were development and validation of a novel automated IGF-1 immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness. Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15ü014 subjects (6697 males and 8317 females, 0-94 years of age). Main Outcome Measures: We measured concentrations of IGF-1 as determined by the IDS iSYS IGF-1 assay. Results: A new IGF-1 assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-1 secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-1 concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals. Conclusions: Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-1 assay. The strict adherence to recent consensus criteria for IGF-1 assays might facilitate clinical application of the results.
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10.
  • Demirkan, Ayse, et al. (författare)
  • Genetic architecture of circulating lipid levels
  • 2011
  • Ingår i: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 19:7, s. 813-819
  • Tidskriftsartikel (refereegranskat)abstract
    • Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
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  • Resultat 1-10 av 26
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