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- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- 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.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.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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- Matt, C. E., et al.
(author)
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Electron scattering, charge order, and pseudogap physics in La1.6-xNd0.4SrxCuO4 : An angle-resolved photoemission spectroscopy study
- 2015
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In: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 92:13
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Journal article (peer-reviewed)abstract
- We report an angle-resolved photoemission study of the charge stripe ordered La1.6-xNd0.4SrxCuO4 (Nd-LSCO) system. A comparative and quantitative line-shape analysis is presented as the system evolves from the overdoped regime into the charge ordered phase. On the overdoped side (x = 0.20), a normal-state antinodal spectral gap opens upon cooling below 80 K. In this process, spectral weight is preserved but redistributed to larger energies. A correlation between this spectral gap and electron scattering is found. A different line shape is observed in the antinodal region of charge ordered Nd-LSCO x = 1/8. Significant low-energy spectral weight appears to be lost. These observations are discussed in terms of spectral-weight redistribution and gapping originating from charge stripe ordering.
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- Küspert, Julia, et al.
(author)
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Pseudogap suppression by competition with superconductivity in La-based cuprates
- 2022
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In: Physical Review Research. - 2643-1564. ; 4:4
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Journal article (peer-reviewed)abstract
- We carried out a comprehensive high-resolution angle-resolved photoemission spectroscopy (ARPES) study of the pseudogap interplay with superconductivity in La-based cuprates. The three systems La2-xSrxCuO4, La1.6-xNd0.4SrxCuO4, and La1.8-xEu0.2SrxCuO4 display slightly different pseudogap critical points in the temperature versus doping phase diagram. We studied the pseudogap evolution into the superconducting state for doping concentrations just below the critical point. In this setting, near optimal doping for superconductivity and in the presence of the weakest possible pseudogap, we uncover how the pseudogap is partially suppressed inside the superconducting state. This conclusion is based on the direct observation of a reduced pseudogap energy scale and re-emergence of spectral weight suppressed by the pseudogap. Altogether these observations suggest that the pseudogap phenomenon in La-based cuprates is in competition with superconductivity for antinodal spectral weight.
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- Horio, M., et al.
(author)
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Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates
- 2018
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:7
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Journal article (peer-reviewed)abstract
- We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k(z) dispersion is observed along the nodal direction, whereas a significant antinodal k(z) dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La2-xSrxCuO4 cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.
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- Kramer, K. P., et al.
(author)
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Band structure of overdoped cuprate superconductors: Density functional theory matching experiments
- 2019
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 99:22
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Journal article (peer-reviewed)abstract
- A comprehensive angle-resolved photoemission spectroscopy study of the band structure in singlelayer cuprates is presented with the aim of uncovering universal trends across different materials. Five different hole-and electron-overdoped cuprate superconductors (La1.59Eu0.2Sr0.21CuO4, La1.77Sr0.23CuO4, Bi1.74Pb0.38Sr1.88CuO6+delta, Tl2Ba2CuO6+delta, and Pr1.15La0.7Ce0.15CuO4) have been studied with special focus on the bands with a predominately d-orbital character. Using a light polarization analysis, the e(g) and t(2g) bands are identified across these materials. A clear correlation between the d(3z2-r2) band energy and the apical oxygen distance d(A) is demonstrated. Moreover, the compound dependence of the d(x2-y2) band bottom and the t(2g) band top is revealed. A direct comparison to density functional theory (DFT) calculations employing hybrid exchange-correlation functionals demonstrates excellent agreement. We thus conclude that the DFT methodology can be used to describe the global band structure of overdoped single-layer cuprates on both the hole-and electron-doped side.
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8. |
- Matt, C. E., et al.
(author)
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Direct observation of orbital hybridisation in a cuprate superconductor
- 2018
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- The minimal ingredients to explain the essential physics of layered copper-oxide (cuprates) materials remains heavily debated. Effective low-energy single-band models of the copper-oxygen orbitals are widely used because there exists no strong experimental evidence supporting multi-band structures. Here, we report angle-resolved photoelectron spectroscopy experiments on La-based cuprates that provide direct observation of a two-band structure. This electronic structure, qualitatively consistent with density functional theory, is parametrised by a two-orbital (d(x2-y2) and d(z2)) tight-binding model. We quantify the orbital hybridisation which provides an explanation for the Fermi surface topology and the proximity of the van-Hove singularity to the Fermi level. Our analysis leads to a unification of electronic hopping parameters for single-layer cuprates and we conclude that hybridisation, restraining d-wave pairing, is an important optimisation element for superconductivity.
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- Riley, J. M., et al.
(author)
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Direct observation of spin-polarized bulk bands in an inversion-symmetric semiconductor
- 2014
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In: Nature Physics. - 1745-2473. ; 10:11, s. 835-839
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Journal article (peer-reviewed)abstract
- Methods to generate spin-polarized electronic states in nonmagnetic solids are strongly desired to enable all-electrical manipulation of electron spins for new quantum devices(1). This is generally accepted to require breaking global structural inversion symmetry(1-5). In contrast, here we report the observation from spin- and angle-resolved photoemission spectroscopy of spin-polarized bulk states in the centrosymmetric transition-metal dichalcogenide WSe2. Mediated by a lack of inversion symmetry in constituent structural units of the bulk crystal where the electronic states are localized(6), we show how spin splittings up to similar to 0.5 eV result, with a spin texture that is strongly modulated in both real and momentum space. Through this, our study provides direct experimental evidence for a putative locking of the spin with the layer and valley pseudospins in transition-metal dichalcogenides(7,8), of key importance for using these compounds in proposed valleytronic devices.
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10. |
- Wang, Qisi, et al.
(author)
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High-Temperature Charge-Stripe Correlations in La1.675Eu0.2Sr0.125CuO4
- 2020
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In: Physical Review Letters. - : AMER PHYSICAL SOC. - 1079-7114 .- 0031-9007. ; 124:18
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Journal article (peer-reviewed)abstract
- We use resonant inelastic x-ray scattering to investigate charge-stripe correlations in La1.675Eu0.2Sr0.125CuO4. By differentiating elastic from inelastic scattering, it is demonstrated that charge-stripe correlations precede both the structural low-temperature tetragonal phase and the transport-defined pseudogap onset. The scattering peak amplitude from charge stripes decays approximately as T-2 towards our detection limit. The in-plane integrated intensity, however, remains roughly temperature independent. Therefore, although the incommensurability shows a remarkably large increase at high temperature, our results are interpreted via a single scattering constituent. In fact, direct comparison to other stripe-ordered compounds (La1.875Ba0.125CuO4, La1.475Nd0.4Sr0.125CuO4, and La1.875Sr0.125CuO4) suggests a roughly constant integrated scattering intensity across all these compounds. Our results therefore provide a unifying picture for the charge-stripe ordering in La-based cuprates. As charge correlations in La1.675Eu0.2Sr0.125CuO4 extend beyond the low-temperature tetragonal and pseudogap phase, their emergence heralds a spontaneous symmetry breaking in this compound.
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