| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Akiba, K., et al.
(författare)
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Measurement of thermal properties of the LHCb VELO detector using track-based software alignment
- 2023
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- The thermal properties of the LHCb Vertex Locator (VELO) are studied using the real-time detector alignment procedure. The variation of the position and orientation of the detector elements as a function of the operating temperature of the VELO is presented. This study uses a dataset collected by the LHCb experiment during a VELO temperature scan performed at the end of LHC Run 2 (October 2018). Significant shrinkage of the VELO modules is observed at the operating temperature of -30(degrees)C compared to the laboratory measurements on a single module taken at a range of temperatures from +45(degrees)C to -25(degrees)C. The thermal shrinkage expected from the extrapolation of laboratory measurements to lower temperatures, and the results of this alignment study are in good agreement.
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| 3. |
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| 4. |
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| 5. |
- Fairfield, Heather, et al.
(författare)
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Mutation discovery in mice by whole exome sequencing
- 2011
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 12:9, s. R86-
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Tidskriftsartikel (refereegranskat)abstract
- We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.
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| 6. |
- Karlson, Björn W., 1953, et al.
(författare)
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A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 117:9, s. 1444-1448
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Tidskriftsartikel (refereegranskat)abstract
- Elevated triglyceride (TG) levels are associated with increased cardiovascular disease risk. In patients with mild-to-moderate hypertriglyceridemia, defined by the European Atherosclerosis Society Consensus Panel as a TG level of 177 to 885 mg/dl (2.0 to 10.0 mmol/L), low-density lipoprotein cholesterol (LDL-C) reduction remains the primary treatment goal. Using data from the indiVidual patient meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin (VOYAGER) meta-analysis, we analyzed LDL-C and TG reductions in patients with baseline TG 2177 mg/dl (>= 2.0 mmol/L). Least squares mean percentage change from baseline in LDL-C and TG was compared using 15,800 patient exposures to rosuvastatin 5 to 40 mg, atorvastatin 10 to 80 mg, and simvastatin 10 to 80 mg in patients with baseline TG >= 177 mg/dl (>= 2.0 mmol/L). Comparisons were made using mixed-effects models with data only from studies directly comparing treatments by randomized design. Mean LDL-C reductions ranged from -26.9% to -55.5%. Rosuvastatin 10 to 40 mg resulted in significantly greater LDL-C reductions than equal or double doses of atorvastatin and simvastatin (p <0.05). Mean TG reductions ranged from -15.1% to -31.3%. Rosuvastatin 10 mg resulted in significantly greater TG reductions than atorvastatin 10 mg (p <0.05). Rosuvastatin 20 and 40 mg resulted in TG reductions similar to those with equal doses of atorvastatin. Rosuvastatin 10 to 40 mg resulted in significantly greater TG reductions than equal or double doses of simvastatin (p <0.05). In conclusion, in patients with hypertriglyceridemia, LDL-C reduction was substantial and dependent on the choice and dose of statin. TG reduction was numerically less than for LDL-C, and additional TG-lowering therapy may be considered to further reduce residual cardiovascular risk. (C) 2016 Elsevier Inc. All rights reserved.
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| 7. |
- Karlson, Björn W., 1953, et al.
(författare)
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Achievement of 2011 European low-density lipoprotein cholesterol (LDL-C) goals of either < 70 mg/dl or >= 50% reduction in high-risk patients: Results from VOYAGER
- 2013
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 228:1, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- Objective Guidelines published in 2011 by the European Atherosclerosis Society and the European Society of Cardiology recommend a goal of either low-density lipoprotein cholesterol (LDL-C) <70 mg/dl (∼1.8 mmol/l) or ≥50% reduction in LDL-C for patients at very high cardiovascular risk. The aim of this study was to determine the percentage of high-risk patients from the VOYAGER individual patient data meta-analysis treated with rosuvastatin 10–40 mg, atorvastatin 10–80 mg or simvastatin 10–80 mg who achieved this goal. Methods We analysed 25,075 patient exposures from high-risk patients. Paired comparisons were made between each rosuvastatin dose and an equal or higher dose of either atorvastatin or simvastatin, with a series of meta-analyses that included only randomised studies that directly compared rosuvastatin and its comparator treatments. Results As statin dose increased, higher percentages of patients achieved LDL-C <70 mg/dl or ≥50% LDL-C reduction. A greater percentage achieved this goal with rosuvastatin 10–40 mg (43.8–79.0%) than with equal or double milligram doses of atorvastatin (16.1–65.2%) or simvastatin (0–39.7%). Paired comparisons showed statistically significant differences for: rosuvastatin 10 mg vs. atorvastatin 10–20 mg and simvastatin 10–20 mg; rosuvastatin 20 mg vs. atorvastatin 20–40 mg and simvastatin 20–80 mg; and rosuvastatin 40 mg vs. atorvastatin 40–80 mg and simvastatin 40–80 mg (all p < 0.001). Conclusion These data from VOYAGER highlight the importance of an effective statin at an appropriate dose to achieve treatment goals for LDL-C in patients with very high cardiovascular risk.
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| 8. |
- Karlson, Björn W., 1953, et al.
(författare)
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Achievement of combined goals of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol with three different statins: Results from VOYAGER
- 2014
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Ingår i: IJC Metabolic and Endocrine. - : Elsevier Ireland Ltd. - 2214-7624. ; 5, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines suggest that the combination of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) is the most clinically relevant goal for lipid-lowering treatments. Methods: Data from VOYAGER, an individual patient data meta-analysis including 32,258 patients from 37 clinical trials, was used to determine the percentage of patients reaching combined goals of LDL-C and non-HDL-C following treatment with simvastatin, atorvastatin, or rosuvastatin. Paired comparisons were made between each dose of rosuvastatin and the same or higher doses of simvastatin and atorvastatin. Results: Each dose of rosuvastatin brought significantly more patients to the combined goal of LDL-C <. 100. mg/dL and non-HDL-C <. 130. mg/dL than the same or double dose of atorvastatin; atorvastatin 80. mg was significantly superior to rosuvastatin 10. mg (all p. <. 0.001). Each dose of rosuvastatin helped significantly more patients reach the combined goal than any dose of simvastatin (all p. <. 0.001), except for rosuvastatin 10. mg versus simvastatin 80. mg (non-significant). Also, each dose of rosuvastatin helped significantly more patients to reach the combined goal of LDL-C <. 70. mg/dL and non-HDL-C <. 100. mg/dL than the same or double dose of atorvastatin (all p. <. 0.001). Every dose of rosuvastatin was significantly superior to all doses of simvastatin (all p. ≤. 0.020), except for rosuvastatin 10. mg versus simvastatin 40. mg and 80. mg (non-significant). Conclusions: Physicians' choice of statin and dose is important in helping patients achieve the combined LDL-C and non-HDL-C goals recommended in established guidelines.
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| 9. |
- Karlson, Björn W., 1953, et al.
(författare)
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Comparison of the effects of different statins and doses on lipid levels in patients with diabetes: Results from VOYAGER
- 2012
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Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 22:9, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Diabetes mellitus is a well-known risk factor for cardiovascular disease, and brings an increased risk of vascular events and a higher mortality rate. Treatment guidelines recommend statins in patients with diabetes, with low-density lipoprotein cholesterol (LDL-C) targets of 100 mg dl(-1) (similar to 2.5 mmol l(-1)), and 80 (similar to 2.0 mmol l(-1)) or 70 mg dl(-1) (similar to 1.8 mmol l(-1)) in especially high-risk patients. The current study used the VOYAGER (an indiVidual patient data-meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin, and simvastatin) database to characterise effects of rosuvastatin, atorvastatin and simvastatin in different doses on lipid levels in diabetes patients. Methods and results: The VOYAGER database included individual patient data from 37 studies involving comparisons of rosuvastatin with either atorvastatin or simvastatin. Of the 32 258 patients included, 8859 (27.5%) had diabetes. Rosuvastatin appeared to be the most efficacious of the three statins, both for lowering LDL-C and for reaching a target level of <70 mg dl(-1) for LDL-C. It was also more effective than atorvastatin at raising high-density lipoprotein cholesterol in the diabetes population. These results are consistent with the overall VOYAGER results. Conclusions: This meta-analysis of 8859 patients with diabetes mellitus shows favourable effects on lipids with the three statins studied, in line with results for the overall VOYAGER population. The importance of using an effective statin at an effective dose to reach treatment goals for such high-risk patients is evident. (c) 2012 Elsevier B.V. All rights reserved.
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| 10. |
- Karlson, Björn W., 1953, et al.
(författare)
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Doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in LDL-C and non-HDL-C: Results from the VOYAGER meta-analysis
- 2016
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:7, s. 744-747
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Tidskriftsartikel (refereegranskat)abstract
- Background Achieving the greatest reduction in atherogenic lipoproteins requires the optimum dose and potency of statin. Using data from the VOYAGER meta-analysis, we determined doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Methods Least squares mean percentage change in LDL-C and non-HDL-C was calculated using 38,052 patient exposures to rosuvastatin 5-40mg, atorvastatin 10-80mg and simvastatin 10-80mg. Equipotent doses were estimated by linear interpolation between actual adjacent doses. Results Rosuvastatin 5mg reduced LDL-C by 39% and non-HDL-C by 35%. Equivalent reductions in LDL-C required atorvastatin 15mg or simvastatin 39mg. Equivalent reductions in non-HDL-C required atorvastatin 14 mg or simvastatin 42mg. Rosuvastatin 10mg reduced LDL-C by 44% and non-HDL-C by 40%. Equivalent reductions in LDL-C required atorvastatin 29 mg or simvastatin 72mg. Equivalent reductions in non-HDL-C required atorvastatin 27 mg or simvastatin 77mg. Rosuvastatin 20mg reduced LDL-C by 50% and non-HDL-C by 45%. Equivalent reductions in LDL-C and non-HDL-C required atorvastatin 70 mg and atorvastatin 62mg, respectively, and were not achieved with the maximum 80mg dose of simvastatin. Rosuvastatin 40mg reduced LDL-C by 55% and non-HDL-C by 50%. Comparable reductions were not achieved with the maximum 80mg doses of atorvastatin or simvastatin. Conclusions Regarding reductions in LDL-C and non-HDL-C, each rosuvastatin dose is equivalent to doses 3-3.5 times higher for atorvastatin and 7-8 times higher for simvastatin.
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