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- Shrine, Nick, et al.
(författare)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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2. |
- Theis-Bröhl, Katharina, et al.
(författare)
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Self-Assembled Layering of Magnetic Nanoparticles in a Ferrofluid on Silicon Surfaces
- 2018
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Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 10:5, s. 5050-5060
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Tidskriftsartikel (refereegranskat)abstract
- This article describes the three-dimensional self assembly of monodisperse colloidal magnetite nanoparticles (NPs) from a dilute water-based ferrofluid onto a silicon surface and the dependence of the resultant magnetic structure on the applied field. The NPs assemble into close-packed layers on the surface followed by more loosely packed ones. The magnetic field-dependent magnetization of the individual NP layers depends on both the rotational freedom of the layer and the magnetization of the adjacent layers. For layers in which the NPs are more free to rotate, the easy axis of the NP can readily orient along the field direction. In more dense packing, free rotation of the NPs is hampered, and the NP ensembles likely build up quasi-domain states to minimize energy, which leads to lower magnetization in those layers. Detailed analysis of polarized neutron reflectometry data together with model calculations of the arrangement of the NPs within the layers and input from small-angle scattering measurements provide full characterization of the core/shell NP dimensions, degree of chaining, arrangement of the NPs within the different layers, and magnetization depth profile.
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3. |
- Yao, Chen, et al.
(författare)
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Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.
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