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| 2. |
- Andersson, Niklas, 1970, et al.
(författare)
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Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men
- 2009
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 33:5, s. 525-533
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Tidskriftsartikel (refereegranskat)abstract
- Context: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. Objective: To systematically investigate our hypotheses that single- nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. Subjects: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n = 1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n = 3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. Main Outcome Measure: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). Results: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 30 untranslated region C4T (rs4252041, minor allele frequency 4%) SNP was associated with the primary outcome total fat mass (P = 0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN_2018 T4C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P = 0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P < 0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. Conclusions: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have no previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men. International Journal of Obesity (2009) 33, 525-533; doi: 10.1038/ijo.2009.47; published online 17 March 2009
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| 4. |
- Ben-Avraham, Dan, et al.
(författare)
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The complex genetics of gait speed : Genome-wide meta-analysis approach
- 2017
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 9:1, s. 209-246
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.
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| 5. |
- Cassel, Björn, et al.
(författare)
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Deflections of an implant-supported cantilever beam subjected to vertically directed loads : in vitro measurements in three dimensions using an optoelectronic method. I. Experimental set-up.
- 2011
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 22:3, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this in vitro study was to develop and test an experimental set-up consisting of a video camera and computer-based optoelectronic motion analysis system, synchronized with a loading device, for studying load-dependent deflections in three dimensions of single implant-supported cantilever beams.Material and methods: One Brånemark System implant was tightly screwed into a steel plate so that the entire implant became submerged. An abutment was attached to the implant and a cast 22-mm-long cantilever gold alloy beam incorporating a prefabricated gold cylinder was attached to the abutment with a prosthetic gold screw. A force transducer was glued on the upper surface of the beam end with its centre 19.4 mm from the centre of the implant abutment gold cylinder unit to register the applied load. A specially designed loading device was used to apply increasing vertical loads of the beam end via the transducer. The motion analysis system was synchronized with the transducer to enable measurements of three-dimensional positional changes of the beam end related to known loads.Results: Vertical loads from 15.7 to 40.4 N were applied resulting in vertical positional changes of the beam end ranging from 40.8 to 225.2 μm (z-axis). The corresponding horizontal changes perpendicular to the long axis of the beam (y-axis) due to counterclockwise horizontal rotation of the beam around the abutment- and prosthetic cylinder threads varied from 7.4 to 77.4 μm. This rotation changed the position of the beam end from 11.9 to 49.3 μm along the x-axis of the coordinate system toward the supporting implant.Conclusion: It was possible to arrange an experimental set-up for optoelectronic 3-D measurements within such a limited measurement volume that would permit satisfactory registrations of small load-dependent deflections of the prosthetic beam and implant components.
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| 6. |
- Cassel, Björn, et al.
(författare)
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Deflections of an implant-supported cantilever beam subjected to vertically directed loads : In vitro measurements in three dimensions using an optoelectronic method. II Analysis of methodological errors.
- 2010
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 22:6, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to evaluate the accuracy, i.e. trueness (validity) and precision (repeatability) for load-dependent deflections in three dimensions of an implant-supported cantilever beam obtained with an optoelectronic motion analysis system compared with a well-known reference method.Materials and methods: A cantilever beam with a length of 22 mm (roughly corresponding to the width of two premolars) was screw-connected to an implant–abutment unit stiffly anchored in a steel plate. The positional changes of beam-end were measured when the beam-end step by step was subjected to four loads, 15.5–40.1 N. This measurement procedure was repeated to comprise six consecutive measurements. The trueness of the method was estimated by comparing the data obtained for vertical deflections with those from a reference method where a hydraulic test system was used to measure the load-deflection ratios of the same beam when subjected to the four mentioned vertical loads.Results: All applied transducer-mediated loads had accuracies (truenesses and repeatabilities below 0.05%). Also, the trueness and precision of the reference method, regarding both movements (deflections) of tested objects and magnitude of applied loads, were tested and found to be high, not exceeding 0.5%.The optoelectronic method however underestimated the smallest vertical deflections for the cantilever beam when compared with the data obtained from the reference method. The underestimation was 26.4%, 15.5% and 8.6% for loads 15.5, 26.6 and 32.6 N, respectively, while there was a slight overestimation of 1.2% for 40.1 N. The precision for the optoelectronic method was found to be for z-axis 1.8 μm, y-axis 3.8 μm and x-axis 1.9 μm.Conclusion: It can be concluded that the trueness (validity) for the optoelectronic method is very high for deflections above 143 μm. The precision (repeatability) of the optoelectronic method was found to be very high.
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| 7. |
- Cassel, Björn, et al.
(författare)
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The influence of stiffness of implant-abutment connection on load-deflection ratios of a screw-retained stiff cantilever beam. 3-D measurements in vitro
- 2013
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 24:11, s. 1251-1256
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The purpose of this in vitro study was to investigate the influence of degree of stiffness of implant-abutment connection of a Brånemark implant system on load- deflection ratios in three dimensions of the beam-end of a screw-retained stiff cantilever beam when subjected to vertically directed loads.Material and methods: Two different implant-abutment connections were tested; welded and screw-retained. One of the abutments (EsthetiCone 2.0; Nobel Biocare AB) was screwed with a torque force of 20 N cm and then laser welded around its entire periphery to one of two Brånemark implants (welded unit). This unit and the other implant were tightly screwed into each of two pre-threaded holes in a steel plate so that the implants became submerged in the plate. The remaining abutment was thereafter screwed to its implant with a torque force of 20 N cm (screw-retained unit). A cantilevered gold beam of 6 mm height and width comprising a gold cylinder (Nobel Biocare AB) was attached to each abutment with a slotted, flat headed, prosthetic gold screw (torque force 10 N cm). A force transducer, synchronized with a 3-D motion analysis system, was glued on the upper surface of each beam-end 19.4 mm from the implant, to register the loads transferred from a specially built loading device. The beam-ends were stepwise subjected to vertically directed loads from 14.9 to 40.3 N and the vertical and horizontal deflections of the beam-ends were registered with the 3-D motion analysis system.Results: For load 14.9–40.3 N the vertical (z-axis) deflections of the beam-end were for the welded implant-abutment connection reduced with 18–46% compared with the screw-retained unit. After maximal loading (40.3 N) the horizontal counter-clockwise rotation of the beam around the screw joints (y-axis rotations) was reduced with 61% for the welded connection. The horizontal movements of the beam-end along the x-axis (x-axis deflections) were reduced with 49% at maximal loading.Conclusion: It was concluded that increased implant-abutment stiffness will substantially reduce both vertical and horizontal deflections of a screw-retained stiff cantilever beam subjected to vertically directed loads.
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| 8. |
- Cawthon, P. M., et al.
(författare)
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Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: AnSDOCAnalysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1429-1437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht(2)); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 +/- 2.3 years for mortality. SETTING Eight prospective observational cohort studies. PARTICIPANTS A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia.
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| 9. |
- Grundberg, Elin, et al.
(författare)
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Population genomics in a disease targeted primary cell model
- 2009
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 19:11, s. 1942-1952
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Tidskriftsartikel (refereegranskat)abstract
- The common genetic variants associated with complex traits typically lie in noncoding DNA and may alter gene regulation in a cell type-specific manner. Consequently, the choice of tissue or cell model in the dissection of disease associations is important. We carried out an expression quantitative trait loci (eQTL) study of primary human osteoblasts (HOb) derived from 95 unrelated donors of Swedish origin, each represented by two independently derived primary lines to provide biological replication. We combined our data with publicly available information from a genome-wide association study (GWAS) of bone mineral density (BMD). The top 2000 BMD-associated SNPs (P < approximately 10(-3)) were tested for cis-association of gene expression in HObs and in lymphoblastoid cell lines (LCLs) using publicly available data and showed that HObs have a significantly greater enrichment (threefold) of converging cis-eQTLs as compared to LCLs. The top 10 BMD loci with SNPs showing strong cis-effects on gene expression in HObs (P = 6 x 10(-10) - 7 x 10(-16)) were selected for further validation using a staged design in two cohorts of Caucasian male subjects. All 10 variants were tested in the Swedish MrOS Cohort (n = 3014), providing evidence for two novel BMD loci (SRR and MSH3). These variants were then tested in the Rotterdam Study (n = 2090), yielding converging evidence for BMD association at the 17p13.3 SRR locus (P(combined) = 5.6 x 10(-5)). The cis-regulatory effect was further fine-mapped to the proximal promoter of the SRR gene (rs3744270, r(2) = 0.5, P = 2.6 x 10(-15)). Our results suggest that primary cells relevant to disease phenotypes complement traditional approaches for prioritization and validation of GWAS hits for follow-up studies.
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| 10. |
- Jones, G., et al.
(författare)
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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p=4x10(-17)), arthritis (GDF5p=4x10(-13)), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
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