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Sökning: WFRF:(Rumley A)

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  • de Vries, Paul S., et al. (författare)
  • Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
  • 2017
  • Ingår i: PLOS ONE. - 1932-6203. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5x10(-8) is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5x10(-8)), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
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  • Wennberg, Patrik, et al. (författare)
  • Haemostatic and inflammatory markers are independently associated with myocardial infarction in men and women
  • 2012
  • Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 129:1, s. 68-73
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Previous studies have shown that plasma levels of haemostatic and inflammatory markers are associated with risk of coronary heart disease (CHD). As haemostatic markers are also acute-phase reactants, it is not clear if their association with CHD is independent of inflammatory markers and established cardiovascular risk factors.MATERIALS AND METHODS: We used a prospective incident case-control study design nested in two cohorts from Sweden. Baseline measurements of a panel of cardiovascular risk factors and eight established markers of haemostasis or inflammation were assessed in 469 first-ever myocardial infarction (MI) cases and 895 matched controls.RESULTS: After adjustment for baseline values of established risk factors, von Willebrand factor appeared to have the strongest association with MI among the haemostatic markers assayed, with an odds ratio of 2.52 (95% CI, 1.72-3.67) for a comparison of individuals in extreme thirds of baseline levels. For a similar comparison, after adjustment for established risk factors and haemostatic markers, odds ratios for IL-6 and CRP were 1.67 (95% CI, 1.08-2.60) and 1.58 (95% CI, 1.03-2.41), respectively. The relative predictive ability of the individual markers over and above established risk factors was modest according to comparisons of Area under the Receiver Operating Characteristic (AUROC) curves. However, when all eight markers were combined in a single model, the AUROC curve was significantly increased to 0.820 (95% CI, 0.795-0.846) compared to 0.762 (95% CI, 0.732-0.791) for established risk factors only.CONCLUSIONS: These findings suggest that haemostasis and inflammation have at least partially separate roles in risk of myocardial infarction.
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