Deformation of LeBrun's ALE metrics with negative mass

In this article we investigate deformations of a scalar-flat K\"ahler metric on the total space of complex line bundles over CP^1 constructed by C. LeBrun. In particular, we find that the metric is included in a one-dimensional family of such metrics on the four-manifold, where the complex structure in the deformation is not the standard one.Comment: 20 pages, no figure. V2: added two references, filled a gap in the proof of Theorem 1.2. V3: corrected a wrong statement about Kuranishi family of a Hirzebruch surface stated in the last paragraph in the proof of Theorem 1.2, and fixed a relevant error in the proof. Also added a reference [24] about Kuranishi family of Hirzebruch surface

Hyperkahler Metrics from Periodic Monopoles

Relative moduli spaces of periodic monopoles provide novel examples of Asymptotically Locally Flat hyperkahler manifolds. By considering the interactions between well-separated periodic monopoles, we infer the asymptotic behavior of their metrics. When the monopole moduli space is four-dimensional, this construction yields interesting examples of metrics with self-dual curvature (gravitational instantons). We discuss their topology and complex geometry. An alternative construction of these gravitational instantons using moduli spaces of Hitchin equations is also described.Comment: 23 pages, latex. v2: an erroneous formula is corrected, and its derivation is given. v3 (published version): references adde

A Conformally Invariant Holographic Two-Point Function on the Berger Sphere

We apply our previous work on Green's functions for the four-dimensional quaternionic Taub-NUT manifold to obtain a scalar two-point function on the homogeneously squashed three-sphere (otherwise known as the Berger sphere), which lies at its conformal infinity. Using basic notions from conformal geometry and the theory of boundary value problems, in particular the Dirichlet-to-Robin operator, we establish that our two-point correlation function is conformally invariant and corresponds to a boundary operator of conformal dimension one. It is plausible that the methods we use could have more general applications in an AdS/CFT context.Comment: 1+49 pages, no figures. v2: Several typos correcte

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10 -6) and rs8057927 in CDH13 (P=1.39 × 10 -5). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10 -7). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10 -7). This signal was replicated in the follow-up analysis (P=2.3 × 10 -2). Significant interaction with maternal CMV infection was found for rs7902091 (P SNP × CMV =7.

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments

Euclid : Impact of non-linear and baryonic feedback prescriptions on cosmological parameter estimation from weak lensing cosmic shear

Upcoming surveys will map the growth of large-scale structure with unprecented precision, improving our understanding of the dark sector of the Universe. Unfortunately, much of the cosmological information is encoded on small scales, where the clustering of dark matter and the effects of astrophysical feedback processes are not fully understood. This can bias the estimates of cosmological parameters, which we study here for a joint analysis of mock Euclid cosmic shear and Planck cosmic microwave background data. We use different implementations for the modelling of the signal on small scales and find that they result in significantly different predictions. Moreover, the different non-linear corrections lead to biased parameter estimates, especially when the analysis is extended into the highly non-linear regime, with the Hubble constant, H0, and the clustering amplitude, σ8, affected the most. Improvements in the modelling of non-linear scales will therefore be needed if we are to resolve the current tension with more and better data. For a given prescription for the non-linear power spectrum, using different corrections for baryon physics does not significantly impact the precision of Euclid, but neglecting these correction does lead to large biases in the cosmological parameters. In order to extract precise and unbiased constraints on cosmological parameters from Euclid cosmic shear data, it is therefore essential to improve the accuracy of the recipes that account for non-linear structure formation, as well as the modelling of the impact of astrophysical processes that redistribute the baryons.Upcoming surveys will map the growth of large-scale structure with unprecented precision, improving our understanding of the dark sector of the Universe. Unfortunately, much of the cosmological information is encoded on small scales, where the clustering of dark matter and the effects of astrophysical feedback processes are not fully understood. This can bias the estimates of cosmological parameters, which we study here for a joint analysis of mock Euclid cosmic shear and Planck cosmic microwave background data. We use different implementations for the modelling of the signal on small scales and find that they result in significantly different predictions. Moreover, the different non-linear corrections lead to biased parameter estimates, especially when the analysis is extended into the highly non-linear regime, with the Hubble constant, H-0, and the clustering amplitude, sigma (8), affected the most. Improvements in the modelling of non-linear scales will therefore be needed if we are to resolve the current tension with more and better data. For a given prescription for the non-linear power spectrum, using different corrections for baryon physics does not significantly impact the precision of Euclid, but neglecting these correction does lead to large biases in the cosmological parameters. In order to extract precise and unbiased constraints on cosmological parameters from Euclid cosmic shear data, it is therefore essential to improve the accuracy of the recipes that account for non-linear structure formation, as well as the modelling of the impact of astrophysical processes that redistribute the baryons.Peer reviewe

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P&lt;10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P&lt;5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health