| 31. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 32. |
- Macdonald-Dunlop, Erin, et al.
(författare)
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Mapping genetic determinants of 184 circulating proteins in 26,494 individuals to connect proteins and diseases
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We performed the largest genome-wide meta-analysis (GWAMA) (Max N=26,494) of the levels of 184 cardiovascular-related plasma protein levels to date and reported 592 independent loci (pQTL) associated with the level of at least one protein (1308 significant associations, median 6 per protein). We estimated that only between 8-37% of testable pQTL overlap with established expression quantitative trait loci (eQTL) using multiple methods, while 132 out of 1064 lead variants show evidence for transcription factor binding, and found that 75% of our pQTL are known DNA methylation QTL. We highlight the variation in genetic architecture between proteins and that proteins share genetic architecture with cardiometabolic complex traits. Using cis-instrument Mendelian randomisation (MR), we infer causal relationships for 11 proteins, recapitulating the previously reported relationship between PCSK9 and LDL cholesterol, replicating previous pQTL MR findings and discovering 16 causal relationships between protein levels and disease. Our MR results highlight IL2-RA as a candidate for drug repurposing for Crohn’s Disease as well as 2 novel therapeutic targets: IL-27 (Crohn’s disease) and TNFRSF14 (Inflammatory bowel disease, Multiple sclerosis and Ulcerative colitis). We have demonstrated the discoveries possible using our pQTL and highlight the potential of this work as a resource for genetic epidemiology.
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| 33. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 34. |
- Nordebo, Sven, et al.
(författare)
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Electromagnetic dispersion modeling and measurements for HVDC power cables
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper provides a general framework for electromagnetic modeling, computation and measurements regarding the wave propagation characteristics of High-Voltage Direct Current (HVDC) power cables. The modeling is focused on very long (10 km or more) HVDC power cables and the relevant frequency range is therefore in the low-frequency regime of about 0-100 kHz. An exact dispersion relation is formulated together with a discussion on practical aspects regarding the computation of the propagation constant and the related characteristic impedance. Experimental time-domain measurement data from an 80 km long HVDC power cable is used to validate the model. It is concluded that a single-mode transmission line model is not adequate to account for the mismatch between the power cable and the instrumentation. A mismatch calibration procedure is therefore devised to account for the connection between the measurement equipment and the cable. A dispersion model is thus obtained that is accurate for early times of pulse arrival. To highlight the potential of accurate electromagnetic modeling, an example of high-resolution length-estimation is discussed and analyzed using statistical methods based on the Cramer-Rao lower bound. The analysis reveals that the estimation accuracy based on the present model (and its related model error) is in the order of 100 m for an 80 km long power cable, and that the potential accuracy using a perfect model based on the given measurement data is in the order of centimeters.
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| 35. |
- Nordebo, Sven, et al.
(författare)
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Low-frequency dispersion characteristics of a multilayered coaxial cable
- 2013
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Ingår i: Journal of Engineering Mathematics. - : Springer Netherlands. - 0022-0833 .- 1573-2703. ; 83:1, s. 169-184
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Tidskriftsartikel (refereegranskat)abstract
- This paper provides an exact asymptotic analysis regarding the low-frequency dispersion characteristics of a multilayered coaxial cable. A layer-recursive description of the dispersion function is derived that is well suited for asymptotic analysis. The recursion is based on two well-behaved (meromorphic) subdeterminants defined by a perfectly electrically conducting (PEC) and a perfectly magnetically conducting termination, respectively. For an open waveguide structure, the dispersion function is a combination of two such functions, and there is only one branch point that is related to the exterior domain. It is shown that if there is one isolating layer and a PEC outer shield, then the classical Weierstrass preparation theorem can be used to prove that the low-frequency behavior of the propagation constant is governed by the square root of the complex frequency, and an exact analytical expression for the dominating term of the asymptotic expansion is derived. It is furthermore shown that the same asymptotic expansion is valid to its lowest order even if the outer shield has finite conductivity and there is an infinite exterior region with finite nonzero conductivity. As a practical application of the theory, a high-voltage direct current (HVDC) power cable is analyzed and a numerical solution to the dispersion relation is validated by comparisons with the asymptotic analysis. The comparison reveals that the low-frequency dispersion characteristics of the power cable is very complicated and a first-order asymptotic approximation is valid only at extremely low frequencies (below 1 Hz). It is noted that the only way to come to this conclusion is to actually perform the asymptotic analysis. Hence, for practical modeling purposes, such as with fault localization, an accurate numerical solution to the dispersion relation is necessary and the asymptotic analysis is useful as a validation tool.
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| 36. |
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| 37. |
- Nordebo, Sven, et al.
(författare)
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Wave modeling and fault localization for underwater power cables
- 2011
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Ingår i: 2011 IEEE-APS Topical Conference on Antennas and Propagation in Wireless Communications (APWC). - : IEEE Press. - 9781457700460 ; , s. 698-701
-
Konferensbidrag (refereegranskat)abstract
- This paper describes some preliminary results regarding Time-Domain pulse Reflection (TDR) measurements and modeling performed on the Baltic Cable submarine HVDC link between southern Sweden and northern Germany. The measurements were conducted in collaboration between the Linnaeus University, Lund University, Baltic Cable AB and ABB High Voltage Cables AB, and is part of the research project: “Fundamental wave modeling for signal estimation on lossy transmission lines”. Preliminary results on measurements and modeling are included here, as well as a first numerical study regarding the low-frequency dispersion characteristics of power cables. The numerical study shows that the finite conductivity of the cable lead shield has a great impact on the losses at low frequencies (0-1 kHz), and that the low-frequency asymptotics of the propagation constant is consistent with common propagation models based on the skin-effect.
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| 38. |
- Persson, Jonas, et al.
(författare)
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Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease
- 2015
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Ingår i: Journal of the American Heart Association. - : WILEY-BLACKWELL. - 2047-9980. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, P<0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.
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| 39. |
- Pettersson, Stefan, 1972, et al.
(författare)
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Off- to in-season body composition adaptations in elite male and female endurance and power event athletics competitors: an observational study
- 2024
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Ingår i: BMC Sports Science, Medicine and Rehabilitation. - : Springer Nature. - 2052-1847. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monitoring elite athletes’ body composition (BC) is vital for health and optimizing performance in sports emphasizing leanness, such as athletics. This study aims to investigate and compare sex- and event-specific off-to in-season BC changes in endurance and power event athletics competitors.Methods: Elite male and female endurance athletes (> 800 m runners; n = 21) and power event athletes (sprinters, jumpers; n = 32) underwent dual-energy X-ray absorptiometry (DXA) scans for whole and regional lean mass (LM), fat mass (FM), bone mineral content (BMC), and density (BMD) during off-season (September-October) and in-season (April-May). Linear mixed models tested between-group off-season differences in BC, within-group off-season to in-season changes, and between-group differences in change. To assess meaningful or least significant changes (LSC) in BC, DXA precision errors were determined from two consecutive total body scans in a subsample of athletes (n = 30).Results: Male athletes (n = 26) gained significantly (p < 0.05) more body mass (BM; mean difference 1.5 [95% confidence interval (CI):0.5–2.4] kg), LM (843 [95% CI:-253:1459] g), and trunk LM (756 [-502:1156] g) than female athletes (n = 27). The proportion of changes in athlete’s BC exceeding the LSC threshold for LM and trunk LM were 70% and 65% in males, and 48% and 26% in females. Significant (p < 0.05) within-group off-season to in-season increases in LM were found for male endurance and power athletes, and female power athletes. All groups significantly increased BMD (p < 0.05). Only male and female power athletes had significant in- to-off-season increases in BMC. 80% of all athletes who had a meaningful increase in BMC belonged to the power event group. No significant within- or between group change in FM was observed.Conclusions: The present study found that male athletes gained more BM, LM and trunk LM than females. Within-group increases in regional and whole-body LM and BMC were predominantly found among power event competitors. Incorporating individual meaningful changes alongside traditional statistics provided additional insights into sex and event-group differences. Future research on elite athletic event groups should include DXA measurements closer to major outdoor-season competitions, coupled with site-specific measures (ultrasound, MRI) for better detection of subtle changes in LM and FM.
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| 40. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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