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- Andersson, Malte, 1941, et al.
(author)
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”Minskande befolkning är inte problemet”
- 2020
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In: Dagens Nyheter. ; :1 augusti, DN-debatt
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Journal article (pop. science, debate, etc.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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- Kilpeläinen, Tuomas O, et al.
(author)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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- Shia-Hui, Peng, 1967, et al.
(author)
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CAA analysis of a wing section with flap side-edges based on hybrid RANS-LES computation
- 2015
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In: 21st AIAA/CEAS Aeroacoustics Conference, AIAA Aviation. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103674
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Conference paper (peer-reviewed)abstract
- Based on hybrid RANS-LES computation of the turbulent flow around a double-flapped wing section, CAA (Computational Aero-Acoustics) analysis was conducted using the Curle, the Kirchhoff and the FW-H acoustic analogy methods. The focus was placed on the flow-induced noise due to the flap side-edges (FSE). It was shown that the FSE has triggered extensive unsteady vortex motions and being the most potent noise-generating source with significant pressure fluctuations on the side-edge surface. In the CAA analysis, two integral surfaces, defined by the iso-surface of vorticity magnitude, were verified when using the Kirchhoff and the FW-H methods. The Kirchhoff method is more sensitive to the location of the integral surface. The analysis using the Curle method indicates that the pressure fluctuations on the surface of the main wing and the first flap have made similar contributions to the far-field noise level, while the second flap contributes slightly less. The Kirchhoff and FW-H methods have predicted overall higher noise levels comparing to the Curle method. In the comparison, the result obtained with a stochastic method based on a RANS solution was also involved. The result has clearly demonstrated that, to capture the most potential noise generation in the presence of flap side edges, turbulence-resolving simulations should be incorporated in hybrid CFD/CAA analysis.
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- Vimaleswaran, Karani S, et al.
(author)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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In: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Journal article (peer-reviewed)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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