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- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 7. |
- Ferguson, M, et al.
(författare)
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Results of the first WHO international collaborative study on the standardization of the detection of antibodies to human papillomaviruses
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 118:6, s. 1508-1514
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Tidskriftsartikel (refereegranskat)abstract
- Detection of genotype-specific human papillomavirus (HPV) capsid antibody in serum suggests past HPV infection. Also, these antibodies appear to correlate with vaccine-induced protection against infection, at least in animal models. However, each laboratory defines a reactive result differently and there is no agreed definition of what level of response indicates sero-reactivity. Standardization of assays for HPV capsid antibody will therefore assist with HPV vaccine development and epidemiology. This study was undertaken to investigate the specificity and sensitivity of assays in current use for measuring antibody to the major viral capsid protein L1 of HPV. Ten laboratories from 8 countries each analyzed 12 coded serum samples, which were derived from an uninfected woman, from naturally infected women and from individuals immunized with different vaccine candidates currently under clinical development. Study samples were assayed by methods in routine use in the participating laboratories. Nine assays were based on virus-like particles (VLPs) of I or more HPV genotypes. One laboratory used bacterially expressed major capsid protein L1 of HPV genotypes as antigen. There was considerable interlaboratory variation in estimated antibody levels. However, ranking of the potency of HPV 16 reactivity across the 12 test sera was consistent for all 10 laboratories. Expression of HPV 16 antibody levels relative to that of a single serum sample from an HPV16-infected woman considerably improved the interlaboratory assay comparability. Establishment of an International Standard for antibodies to HPV 16 would therefore facilitate the comparison of HPV antibody measurements between laboratories and assays. (c) 2005 Wiley-Liss, Inc.
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- Wilhelmsen, Lars, 1932, et al.
(författare)
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SLCO1B1 variants and statin-induced myopathy--a genomewide study.
- 2008
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Ingår i: The New England journal of medicine. - 1533-4406. ; 359:8, s. 789-99
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. METHODS: We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. RESULTS: The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r(2)=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. CONCLUSIONS: We have identified common variants in SLCO1B1 that are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively. (Current Controlled Trials number, ISRCTN74348595.)
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- Bannon, L., et al.
(författare)
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Hybrid design creates innovative, museum experiences
- 2005
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Ingår i: Communications of the ACM. - : Association for Computing Machinery (ACM). - 0001-0782 .- 1557-7317. ; 48:3, s. 62-65
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Tidskriftsartikel (refereegranskat)abstract
- Museums which rely on simple text panels for providing information to visitors about museum artifacts are discussed. The study involved extensive fieldwork, audio-visual recording, interviews and discussion with curators, museum, educators and exhibit designers. The radio frequency identification (RFID)-tagged paper enabled visitors to assemble a coherent experience from their interactions with different installations. It is suggested that ubiquitous technologies should be assembled and combined with other media to form a interactive and collaborative systems in the museum.
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