Human population structure, genome autozygosity and human health

A major transition in human population structure is currently under way, moving from a historical metapopulation, comprising small and mainly rural endogamous communities, to large and increasingly panmictic urban populations. This process is predicted to increase outbreeding, and preliminary data from genomic surveys have helped to quantify the potential magnitude of the effects. Population genetic trends of this nature should result in a reduced burden of recessive disorders, and have a favourable impact on complex diseases influenced by partially recessive genetic variants of smaller effect. The overall outcome is expected to be beneficial for a range of traits associated with human health and disease that show dominance variance

West Nile Virus Infections Projected from Blood Donor Screening Data, United States, 2003

Routine donor nucleic acid amplification testing is a valuable surveillance screening tool

KiDS-1000: Combined halo-model cosmology constraints from galaxy abundance, galaxy clustering, and galaxy-galaxy lensing

We present constraints on the flat Λ cold dark matter cosmological model through a joint analysis of galaxy abundance, galaxy clustering, and galaxy-galaxy lensing observables with the Kilo-Degree Survey. Our theoretical model combines a flexible conditional stellar mass function, which describes the galaxy-halo connection, with a cosmological N-body simulation-calibrated halo model, which describes the non-linear matter field. Our magnitude-limited bright galaxy sample combines nine-band optical-to-near-infrared photometry with an extensive and complete spectroscopic training sample to provide accurate redshift and stellar mass estimates. Our faint galaxy sample provides a background of accurately calibrated lensing measurements. We constrain the structure growth parameter to S8 = σ8√Ωm/0.3 =√0.773−0.030+0.028 and the matter density parameter to Ωm = 0.290−0.017+0.021. The galaxy-halo connection model adopted in the work is shown to be in agreement with previous studies. Our constraints on cosmological parameters are comparable to, and consistent with, joint ‘3 × 2pt’ clustering-lensing analyses that additionally include a cosmic shear observable. This analysis therefore brings attention to the significant constraining power in the often excluded non-linear scales for galaxy clustering and galaxy-galaxy lensing observables. By adopting a theoretical model that accounts for non-linear halo bias, halo exclusion, scale-dependent galaxy bias, and the impact of baryon feedback, this work demonstrates the potential for, and a way towards, including non-linear scales in cosmological analyses. Varying the width of the satellite galaxy distribution with an additional parameter yields a strong preference for sub-Poissonian variance, improving the goodness of fit by 0.18 in terms of the reduced χ2 value (and increasing the p-value by 0.25) compared to a fixed Poisson distribution

KiDS-1000: Combined halo-model cosmology constraints from galaxy abundance, galaxy clustering and galaxy-galaxy lensing

We present constraints on the flat $\Lambda$CDM cosmological model through a joint analysis of galaxy abundance, galaxy clustering and galaxy-galaxy lensing observables with the Kilo-Degree Survey. Our theoretical model combines a flexible conditional stellar mass function, to describe the galaxy-halo connection, with a cosmological N-body simulation-calibrated halo model to describe the non-linear matter field. Our magnitude-limited bright galaxy sample combines 9-band optical-to-near-infrared photometry with an extensive and complete spectroscopic training sample to provide accurate redshift and stellar mass estimates. Our faint galaxy sample provides a background of accurately calibrated lensing measurements. We constrain the structure growth parameter $S_8=\sigma_8\sqrt{\Omega_{\mathrm{m}}/0.3}=0.773^{+0.028}_{-0.030}$, and the matter density parameter $\Omega_{\mathrm{m}}=0.290^{+0.021}_{-0.017}$. The galaxy-halo connection model adopted in the work is shown to be in agreement with previous studies. Our constraints on cosmological parameters are comparable to, and consistent with, joint $3\times2{\mathrm{pt}}$ clustering-lensing analyses that additionally include a cosmic shear observable. This analysis therefore brings attention to the significant constraining power in the often-excluded non-linear scales for galaxy clustering and galaxy-galaxy lensing observables. By adopting a theoretical model that accounts for non-linear halo bias, halo exclusion, scale-dependent galaxy bias and the impact of baryon feedback, this work demonstrates the potential and a way forward to include non-linear scales in cosmological analyses. Varying the width of the satellite galaxy distribution with an additional parameter yields a strong preference for sub-Poissonian variance, improving the goodness of fit by 0.18 in reduced $\chi^{2}$ value compared to a fixed Poisson distribution.Comment: 25 pages, 16 figures, accepted for publication in A&

Organised Randoms: learning and correcting for systematic galaxy clustering patterns in KiDS using self-organising maps

We present a new method for the mitigation of observational systematic effects in angular galaxy clustering via corrective random galaxy catalogues. Real and synthetic galaxy data, from the Kilo Degree Survey's (KiDS) 4$^{\rm{th}}$ Data Release (KiDS-$1000$) and the Full-sky Lognormal Astro-fields Simulation Kit (FLASK) package respectively, are used to train self-organising maps (SOMs) to learn the multivariate relationships between observed galaxy number density and up to six systematic-tracer variables, including seeing, Galactic dust extinction, and Galactic stellar density. We then create `organised' randoms, i.e. random galaxy catalogues with spatially variable number densities, mimicking the learnt systematic density modes in the data. Using realistically biased mock data, we show that these organised randoms consistently subtract spurious density modes from the two-point angular correlation function $w(\vartheta)$, correcting biases of up to $12\sigma$ in the mean clustering amplitude to as low as $0.1\sigma$, over a high signal-to-noise angular range of 7-100 arcmin. Their performance is also validated for angular clustering cross-correlations in a bright, flux-limited subset of KiDS-$1000$, comparing against an analogous sample constructed from highly-complete spectroscopic redshift data. Each organised random catalogue object is a `clone' carrying the properties of a real galaxy, and is distributed throughout the survey footprint according to the parent galaxy's position in systematics-space. Thus, sub-sample randoms are readily derived from a single master random catalogue via the same selection as applied to the real galaxies. Our method is expected to improve in performance with increased survey area, galaxy number density, and systematic contamination, making organised randoms extremely promising for current and future clustering analyses of faint samples.Comment: 18 pages (6 appendix pages), 12 figures (8 appendix figures), submitted to A&

Clustering of red-sequence galaxies in the fourth data release ofthe Kilo-Degree Survey

We present a sample of luminous red-sequence galaxies to study the large-scale structure in the fourth data release of the Kilo-Degree Survey. The selected galaxies are defined by a red-sequence template, in the form of a data-driven model of the colour-magnitude relation conditioned on redshift. In this work, the red-sequence template is built using the broad-band optical+near infrared photometry of KiDS-VIKING and the overlapping spectroscopic data sets. The selection process involves estimating the red-sequence redshifts, assessing the purity of the sample, and estimating the underlying redshift distributions of redshift bins. After performing the selection, we mitigate the impact of survey properties on the observed number density of galaxies by assigning photometric weights to the galaxies. We measure the angular two-point correlation function of the red galaxies in four redshift bins, and constrain the large scale bias of our red-sequence sample assuming a fixed $\Lambda$CDM cosmology. We find consistent linear biases for two luminosity-threshold samples (dense and luminous). We find that our constraints are well characterized by the passive evolution model.Comment: submitted to A&

An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males

<p>Abstract</p> <p>Background</p> <p>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.</p> <p>Methods</p> <p>We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.</p> <p>Results</p> <p>One SNP, rs17321050, in the transducin β-like 1X-linked (<it>TBL1X</it>) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (<it>P </it>value = 4.86 × 10^-6) and joint analysis (<it>P </it>value = 4.53 × 10^-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (<it>P </it>= 5.89 × 10^-3) and passed the replication threshold in the validation data set (<it>P </it>= 2.56 × 10^-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.</p> <p>Conclusions</p> <p><it>TBL1X </it>is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing <it>TBL1X </it>and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that <it>TBL1X </it>may play a role in ASD risk.</p

Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates

Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise epistasis signals in SUA levels. In the resultant epistasis profile, no SNP pairs reached the Bonferroni adjusted threshold for the pair-wise genome-wide significance. However, SLC2A9 was found interacting with multiple loci across the genome, with NFIA - SLC2A9 and SLC2A9 - ESRRAP2 being significant based on a threshold derived for interactions between GWA significant SNPs and the genome and jointly explaining 8.0% of the phenotypic variance in SUA levels (3.4% by interaction components). Epistasis signal replication in a CROATIAN population (n = 1772) was limited at the SNP level but improved dramatically at the gene ontology level. In addition, gene ontology terms enriched by the epistasis signals in each population support links between SUA levels and neurological disorders. We conclude that GWA epistasis analysis is useful despite relatively low power in small isolated populations

A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations:the EUROSPAN project

We set out to identify common genetic determinants of the length of the RR and QT intervals in 2325 individuals from isolated European populations.We analyzed the heart rate at rest, measured as the RR interval, and the length of the corrected QT interval for association with 318 237 single-nucleotide polymorphisms. The RR interval was associated with common variants within GPR133, a G-protein-coupled receptor (rs885389, P=3.9 x 10(-8)). The QT interval was associated with the earlier reported NOS1AP gene (rs2880058, P=2.00 x 10(-10)) and with a region on chromosome 13 (rs2478333, P=4.34 x 10(-8)), which is 100 kb from the closest known transcript LOC730174 and has previously not been associated with the length of the QT interval.Our results suggested an association between the RR interval and GPR133 and confirmed an association between the QT interval and NOS1AP