| 221. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 222. |
- Peloso, Gina M, et al.
(författare)
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Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
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| 223. |
- Postmus, Iris, et al.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 224. |
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| 225. |
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| 226. |
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| 227. |
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| 228. |
- Siggeirsdottir, K., et al.
(författare)
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Epidemiology of fractures in Iceland and secular trends in major osteoporotic fractures 1989-2008
- 2014
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of the most common fracture types in Iceland is reported based on individual data from the Reykjavik Study 1967-2008. Time trend is reported for the major osteoporotic fractures (MOS) 1989-2008. This study aims to assess the incidence of all fractures in Iceland, with emphasis on the rate of hip fractures, and compare the incidence with other populations as well as examine the secular changes. Individuals from the prospective population-based cohort Reykjavik Study were examined between 1967 and 2008 (follow-up 26.5 years), which consisted of 9,116 men and 9,756 women born in 1907-1935, with age range 31-81 years. First fracture incidence was estimated using life table methods with age as the timescale. Fracture rate increased proportionally with age between the sexes for vertebral and proximal humerus but disproportionally for hip and distal forearm fractures. The ratio of first fracture incidence between the sexes varied considerably by site: 2.65 for hip fractures and the highest for distal forearm fractures at 4.83. By the age of 75, 36.7 % of women and 21 % of men had sustained a fracture, taking into account competing risk of death. The incidence of hip fractures was similar to results previously published from USA, Sweden, Norway, and Scotland. The incidence of MOS fractures in both sexes decreased over the last decade, except hip fractures in men, which remained unchanged, as reflected in the women/men ratio for the hip, which changed from 2.6 to 1.7. This study adds information to scarce knowledge on the relative fracture incidence of different fractures. The incidence of MOS fractures increased in the latter part of the last century in both sexes and declined during the last decade, less dramatically for men. This information is important for planning health resources.
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| 229. |
- Siggeirsdottir, K, et al.
(författare)
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Short hospital stay augmented with education and home-based rehabilitation improves function and quality of life after hip replacement - Randomized study of 50 patients with 6 months of follow-up
- 2005
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 76:4, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- Background Because of current cost restrictions, we studied the effect of a shorter hospital stay on function, pain and quality of life (QOL) after total hip replacement (THR). Patients and methods 50 patients from two hospitals were randomized into a study group (SG) of 27 patients receiving preoperative and postoperative education programs, as well as home visits from an outpatient team, and a control group (CG) of 23 patients receiving "conventional" rehabilitation often augmented by a stay at a rehabilitation center. Results Mean hospital stay was shorter for the SG than for the CG (6.4 days and 10 days, respectively; p < 0.001). During the 6-month study period, there were 9 non-fatal complications in the SG and 12 in the CG (p = 0.3). The difference in Oxford Hip Score between the groups was not statistically significant before the operation, but was better for the SG at 2 months (p = 0.03) and this difference remained more or less constant throughout the study. The overall score from the Nottingham Health Profile indicated a better QOL in the SG. Interpretation Our preoperative education program, followed by postoperative home-based rehabilitation, appears to be safer and more effective in improving function and QOL after THR than conventional treatment.
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| 230. |
- Siggeirsdottir, K., et al.
(författare)
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The incidence of a first major osteoporotic fracture in Iceland and implications for FRAX
- 2014
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 25:10, s. 2445-2451
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Tidskriftsartikel (refereegranskat)abstract
- Based on an extensive cohort study over 25 years, the present study supports the assumption that major osteoporotic fractures can be reasonably predicted from hip fracture rates. The construct for FRAX models depends on algorithms to adjust for double counting of fracture outcomes in some models and in others, to estimate the incidence of a major fracture from hip fracture rates. The aim of the present study was to test the validity of these algorithms in a large prospective cohort. The incidence of hip, clinical spine, distal forearm, and humerus fracture was determined in the prospective and ongoing population-based Reykjavik Study with follow up of 257,001 person-years. The incidence of a first major fracture was compared with the correction factors used in FRAX to adjust the incidence of several fracture outcomes for double counting. In addition, the incidence of a major osteoporotic fracture estimated from the Icelandic hip fracture rates was compared with the Malmo ratios used in FRAX. The adjustments necessary to account for multiple fracture outcomes were similar to those previously derived from Sweden. Additionally, incidence of a first major osteoporotic fracture was similar to that derived for FRAX models. The findings of the present study support the algorithms used in FRAX to estimate the incidence of a first major fracture and the predictive value of hip fracture for other major fractures.
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