Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture

The heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h2 = 26.3%, 95% CI 23.7–29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p<5 × 10-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 × 10-9) but failed to replicate variants previously associated with TB susceptibility. These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressure

The Dependence of the Superconducting Transition Temperature of Organic Molecular Crystals on Intrinsically Non-Magnetic Disorder: a Signature of either Unconventional Superconductivity or Novel Local Magnetic Moment Formation

We give a theoretical analysis of published experimental studies of the effects of impurities and disorder on the superconducting transition temperature, T_c, of the organic molecular crystals kappa-ET_2X and beta-ET_2X (where ET is bis(ethylenedithio)tetrathiafulvalene and X is an anion eg I_3). The Abrikosov-Gorkov (AG) formula describes the suppression of T_c both by magnetic impurities in singlet superconductors, including s-wave superconductors and by non-magnetic impurities in a non-s-wave superconductor. We show that various sources of disorder lead to the suppression of T_c as described by the AG formula. This is confirmed by the excellent fit to the data, the fact that these materials are in the clean limit and the excellent agreement between the value of the interlayer hopping integral, t_perp, calculated from this fit and the value of t_perp found from angular-dependant magnetoresistance and quantum oscillation experiments. If the disorder is, as seems most likely, non-magnetic then the pairing state cannot be s-wave. We show that the cooling rate dependence of the magnetisation is inconsistent with paramagnetic impurities. Triplet pairing is ruled out by several experiments. If the disorder is non-magnetic then this implies that l>=2, in which case Occam's razor suggests that d-wave pairing is realised. Given the proximity of these materials to an antiferromagnetic Mott transition, it is possible that the disorder leads to the formation of local magnetic moments via some novel mechanism. Thus we conclude that either kappa-ET_2X and beta-ET_2X are d-wave superconductors or else they display a novel mechanism for the formation of localised moments. We suggest systematic experiments to differentiate between these scenarios.Comment: 18 pages, 5 figure

Wideband on-chip terahertz spectrometer based on a superconducting filterbank

Instrumentatio

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia

Measurement of the longitudinal diffusion of ionization electrons in the MicroBooNE detector

Abstract: Accurate knowledge of electron transport properties is vital to understanding the information provided by liquid argon time projection chambers (LArTPCs). Ionization electron drift-lifetime, local electric field distortions caused by positive ion accumulation, and electron diffusion can all significantly impact the measured signal waveforms. This paper presents a measurement of the effective longitudinal electron diffusion coefficient, DL, in MicroBooNE at the nominal electric field strength of 273.9 V/cm. Historically, this measurement has been made in LArTPC prototype detectors. This represents the first measurement in a large-scale (85 tonne active volume) LArTPC operating in a neutrino beam. This is the largest dataset ever used for this measurement. Using a sample of ∼70,000 through-going cosmic ray muon tracks tagged with MicroBooNE's cosmic ray tagger system, we measure DL = 3.74+0.28 -0.29 cm2/s

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH