Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently... Show moreBackground: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk. Show less
Goyal, A.; Bondü, C.J.; Graf, M.; Koper, M.T.M. 2022
Plasmonic photocatalysis via hot charge carriers suffers from their short lifetime compared with the sluggish kinetics of most reactions. To increase lifetime, adsorbates on the surface of a... Show morePlasmonic photocatalysis via hot charge carriers suffers from their short lifetime compared with the sluggish kinetics of most reactions. To increase lifetime, adsorbates on the surface of a plasmonic metal may create preferential states for electrons to be excited from. We demonstrate this effect with O adsorbates on a nanoporous gold electrode. Nanoporous gold is used to obtain a broadband optical response, to increase the obtained photocurrent, and to provide a SERS-active substrate. Only with adsorbates present, we observe significant photocurrents. Illumination also increases the adsorbate coverage above its dark potential-dependent equilibrium, as derived from a two-laser in situ SERS approach. Density functional theory calculations confirm the appearance of excitable states below the Fermi level. The photocurrent enhancement and broadband characteristics reveal the potential of the plasmonic approach to improve the efficiency of photoelectrochemical water splitting. Show less
Bondü, C.J.; Graf, M.; Goyal, A.; Koper, M.T.M. 2020
In this article we investigate the electrochemical reduction of CO2 at gold electrodes under mildly acidic conditions. Differential electrochemical mass spectroscopy (DEMS) is used to quantify the... Show moreIn this article we investigate the electrochemical reduction of CO2 at gold electrodes under mildly acidic conditions. Differential electrochemical mass spectroscopy (DEMS) is used to quantify the amounts of formed hydrogen and carbon monoxide as well as the consumed amount of CO2. We investigate how the Faradaic efficiency of CO formation is affected by the CO2 partial pressure (0.1-0.5 bar) and the proton concentration (1-0.25 mM). Increasing the former enhances the rate of CO2 reduction and suppresses hydrogen evolution from proton reduction, leading to Faradaic efficiencies close to 100%. Hydrogen evolution is suppressed by CO2 reduction as all protons at the electrode surfaces are used to support the formation of water (CO2 + 2H(+) + 2e(-) -> CO + H2O). Under conditions of slow mass transport, this leaves no protons to support hydrogen evolution. On the basis of our results, we derive a general design principle for acid CO2 electrolyzers to suppress hydrogen evolution from proton reduction: the rate of CO/OH- formation must be high enough to match/compensate the mass transfer of protons to the electrode surface. Show less
