Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions... Show moreCommon single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. Show less
The development of energy conversion systems depends strongly on our fundamental understanding of the electrochemical interface of the electrocatalyst. Here, we study the changes in the surface... Show moreThe development of energy conversion systems depends strongly on our fundamental understanding of the electrochemical interface of the electrocatalyst. Here, we study the changes in the surface morphology of a platinum polycrystalline electrode during oxidation-reduction cycles in a wide potential window (0.05-2.0 V) in sodium hydroxide by in situ atomic force microscopy. Platinum nanoparticles are observed on the surface after cycling due to the redeposition of dissolved platinum ions. The influence of scan rate on platinum redeposition is studied by applying asymmetric potential sweep programs. The negative-going scan rate is the key factor here, as it controls the reduction of platinum oxide, as well as the redeposition of platinum. Moreover, it is found that chloride ions in the electrolyte impede the redeposition by complexing with platinum. This investigation enables us to reveal the surface roughening processes on platinum electrode in alkaline electrolyte and assists in understanding the fundamentals of the stability of platinum-containing energy conversion systems. Show less
A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene... Show moreA person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. Show less
Understanding the electrochemical behavior of Pt at the solid/liquid interface is of significant importance for the development of efficient electrochemical devices, such as fuel cells and water... Show moreUnderstanding the electrochemical behavior of Pt at the solid/liquid interface is of significant importance for the development of efficient electrochemical devices, such as fuel cells and water electrolyzers. In this work, the evolution of the surface morphology of a polycrystalline platinum under potential cycling condition was investigated by in situ electrochemical atomic force microscopy (EC-AFM). After 50 cycles between 0.05-1.8 V in 0.1 M H2SO4, the Pt surface is coarsened and nanoparticles of several nanometers appear on the surface. The critical upper and lower potential for the formation of nanoparticles are found to be 1.8 and 0.8 V, respectively. The in situ AFM observation coupled with CV reveals the periodic disappearance and reappearance of the nanoparticles, based on which the formation of nanoparticles is attributed to the deposition of dissolved Pt from solution, and a model for the nanoparticle formation is proposed. While the formation of a thick oxide layer is a prerequisite, the reduction process is found to have a strong influence on Pt nanoparticles formation as well. This investigation provides a visualization of the Pt electrode surface under electrochemical control in a large potential window, enabling a broader understanding of the Pt electrode roughening mechanisms. Show less
