| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 4. |
- Poppi, Stefano, et al.
(författare)
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Analysis of system improvements in solar thermal and air source heat pump combisystems
- 2016
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Ingår i: Applied Energy. - : Elsevier. - 0306-2619 .- 1872-9118. ; 173, s. 606-623
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Tidskriftsartikel (refereegranskat)abstract
- A solar thermal and heat pump combisystem is one of many system alternatives on the market for supplying domestic hot water (DHW) and space heating (SH) in dwellings. In this study a reference solar thermal and air source heat pump combisystem was defined and modelled based on products available on the market. Based on the results of an extensive literature survey, several system variations were investigated to show the influence of heat pump cycle, thermal storage and system integration on the use of electricity for two houses in the climates of Zurich and Carcassonne. A singular economic cash flow analysis was carried out and the "additional investment limit" of each system variation was determined for a range of economic boundary conditions. This is the maximum extra investment cost for the system variant compared to the reference system that will give a break even result for a 10 year period. The results show that variations in electricity price affects the additional investment limit far more than the other economic parameters. Several of the variants show potential for achieving a cost benefit, but the potential varies a lot depending on load and climate boundary conditions. For all variants, the biggest difference in electricity savings was found for Zurich rather than in Carcassonne, which is explained by the larger heating load. However, in three cases the largest savings were for the SFH45 house despite the fact that the annual electricity use of the system is much lower than that for the SFH100 house, 3581 kW h/year compared to 8340 kW h/year. This was attributed to the fact that, in these cases, the operating level of the space heating circuit played a significant role, the SFH45 house being supplied with a 35/30 °C heating system while the SFH100 was supplied with a 55/45 °C heating system.
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| 5. |
- Poppi, Stefano, et al.
(författare)
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Influence of boundary conditions and component size on electricity demand in solar thermal and heat pump combisystems
- 2016
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Ingår i: Applied Energy. - : Elsevier. - 0306-2619 .- 1872-9118. ; 162, s. 1062-1073
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Tidskriftsartikel (refereegranskat)abstract
- Solar thermal and heat pump combisystems are used to produce domestic hot water (DHW) and space heating (SH) in dwellings. Many systems are available on the market. For an impartial comparison, a definite level of thermal comfort should be defined and ensured in all systems. This work studied the influence of component size on electricity demand for a state of the art solar thermal and heat pump system. A systematic series of parametric studies was carried out by using TRNSYS to show the impact of climate, load and size of main components as well as heat source for the heat pump. Penalty functions were used to ensure that all variations provided the same comfort requirements. Two reference systems were defined and modelled based on products on the market, one with ambient air and the other with borehole as heat source for the heat pump. The results show that changes in collector area from 5 to 15m2 result in a decrease in system electricity of between 305 and 552kWh/year. Changes in heat exchanger size for DHW preparation were shown to give nearly as large changes in electricity use due to the fact that the set temperature in the store was changed to give the same thermal comfort in all cases. Decrease in heat pump size was shown to give a decrease in electricity use for the ASHP in the building with larger heat demand while it increased or had only a small change for other boundary conditions. Heat pump losses were shown to be an important factor highlighting the importance of modelling this factor explicitly.
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