| 1. |
- Do, Ron, et al.
(författare)
-
Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
-
Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
|
|
| 2. |
- Willer, Cristen J., et al.
(författare)
-
Discovery and refinement of loci associated with lipid levels
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
-
Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
|
|
| 3. |
|
|
| 4. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 5. |
- Hyldegaard, S., et al.
(författare)
-
R-matrix analysis of the beta decays of 12N and 12B
- 2010
-
Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 81:2
-
Tidskriftsartikel (refereegranskat)abstract
- The β decays of 12N and 12B have been studied at KVI and JYFL to resolve the composition of the broad and interfering 0+ and 2+ strengths in the triple-α continuum. For the first time a complete treatment of 3α decay is presented including all major breakup channels. A multilevel, many-channel R-matrix formalism has been developed for the complete description of the breakup in combination with the recently published separate analysis of angular correlations. We find that, in addition to the Hoyle state at 7.65 MeV, more than one 0+ and 2+ state is needed to reproduce the spectra. Broad 03+ and 22+ states are found between 10.5 and 12 MeV in this work. The presence of β strength up to the 12N Q-value window suggests the presence of additional 0+ and 2+ components in the 12C structure at energies above 12.7 MeV.
|
|
| 6. |
|
|
| 7. |
- Enkovaara, J., et al.
(författare)
-
Electronic structure calculations with GPAW : a real-space implementation of the projector augmented-wave method
- 2010
-
Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 22:25, s. 253202-
-
Forskningsöversikt (refereegranskat)abstract
- Electronic structure calculations have become an indispensable tool in many areas of materials science and quantum chemistry. Even though the Kohn-Sham formulation of the density-functional theory (DFT) simplifies the many-body problem significantly, one is still confronted with several numerical challenges. In this article we present the projector augmented-wave (PAW) method as implemented in the GPAW program package (https://wiki.fysik.dtu.dk/gpaw) using a uniform real-space grid representation of the electronic wavefunctions. Compared to more traditional plane wave or localized basis set approaches, real-space grids offer several advantages, most notably good computational scalability and systematic convergence properties. However, as a unique feature GPAW also facilitates a localized atomic-orbital basis set in addition to the grid. The efficient atomic basis set is complementary to the more accurate grid, and the possibility to seamlessly switch between the two representations provides great flexibility. While DFT allows one to study ground state properties, time-dependent density-functional theory (TDDFT) provides access to the excited states. We have implemented the two common formulations of TDDFT, namely the linear-response and the time propagation schemes. Electron transport calculations under finite-bias conditions can be performed with GPAW using non-equilibrium Green functions and the localized basis set. In addition to the basic features of the real-space PAW method, we also describe the implementation of selected exchange-correlation functionals, parallelization schemes, Delta SCF-method, x-ray absorption spectra, and maximally localized Wannier orbitals.
|
|
| 8. |
- Granér, Marit, et al.
(författare)
-
Cardiac steatosis associates with visceral obesity in nondiabetic obese men.
- 2013
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:3, s. 1189-97
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Liver fat and visceral adiposity are involved in the development of the metabolic syndrome (MetS). Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. The aim of this study was to explore components of cardiac steatosis and their relationship to intra-abdominal ectopic fat deposits and cardiometabolic risk factors in nondiabetic obese men. Methods: Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy, and visceral adipose (VAT), abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by magnetic resonance imaging in 37 men with the MetS and in 40 men without the MetS. Results: Myocardial and hepatic TG contents, VAT, SAT, epicardial fat volumes, and pericardial fat volumes were higher in men with the MetS compared with subjects without the MetS (P < .001). All components of cardiac steatosis correlated with SAT, VAT, and hepatic TG content and the correlations seemed to be strongest with VAT. Myocardial TG content, epicardial fat, pericardial fat, VAT, and hepatic TG content correlated with waist circumference, body mass index, high-density lipoprotein cholesterol TGs, very low-density lipoprotein-1 TGs, and the insulin-resistance homeostasis model assessment index. VAT was a predictor of TGs, high-density lipoprotein cholesterol, and measures of glucose metabolism, whereas age and SAT were determinants of blood pressure parameters. Conclusions: We suggest that visceral obesity is the best predictor of epicardial and pericardial fat in abdominally obese subjects. Myocardial TG content may present a separate entity that is influenced by factors beyond visceral adiposity.
|
|
| 9. |
- Graner, M., et al.
(författare)
-
Cardiac steatosis in patients with dilated cardiomyopathy
- 2014
-
Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:14
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. Limited data exist on cardiac adiposity in subjects with dilated cardiomyopathy (DCM). The aim of the study was to examine the components of cardiac steatosis and their relationship to LV structure and function in non-diabetic DCM patients. Methods Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy (MRS), and LV function, visceral adipose (VAT) and abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MRI in 10 non-diabetic men with DCM and in 20 controls. Results In face of comparable intra-abdominal fat depots, myocardial TG [0.41% (0.21-2.19) vs 0.86% (0.31-2.24), p=0.038] was markedly lower and epicardial (895 mm(2)+/- 110 vs 664 mm(2)+/- 180, p=0.002) and pericardial fat [2173 mm(2) (616-3673) vs 1168 mm(2) (266-2319), p=0.039] depots were larger in patients with DCM compared with controls. In subjects with DCM, the LV global function index was decreased to a greater extent than the LV EF [21%+/- 6 vs 34% (16-40)]. Conclusions Myocardial TG content decreased and epicardial and pericardial fat depots increased in non-diabetic subjects with DCM. Although recognised as a site of ectopic fat accumulation, the derangement of myocardial TG seems to play a specific role in the myocardial energy metabolism in congestive heart failure.
|
|
| 10. |
- Heid, Iris M, et al.
(författare)
-
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
|
|
