People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found ...evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.
Summary
Background
Specific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and ...asthma risk.
Objective
To define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen‐specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk.
Methods
Children at high‐risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen‐specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap® 100; Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years.
Results
Sensitization to dog was strongly associated with increased asthma risk (P < 0.0001). Sensitization to perennial compared with seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (P = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (P = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (P = 0.05).
Conclusions and Clinical Relevance
Analysing specific patterns of an individual's allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as ‘atopic’ by the presence of any demonstrable sensitization alone. Furthermore, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of sensitization.
The Earth’s thermosphere and ionosphere constitute a dynamic system that varies daily in response to energy inputs from above and from below. This system can exhibit a significant response within an ...hour to changes in those inputs, as plasma and fluid processes compete to control its temperature, composition, and structure. Within this system, short wavelength solar radiation and charged particles from the magnetosphere deposit energy, and waves propagating from the lower atmosphere dissipate.
Understanding the global-scale response of the thermosphere-ionosphere
(
T-I
)
system to these drivers is essential to advancing our physical understanding of coupling between the space environment and the Earth’s atmosphere
. Previous missions have successfully determined how the “climate” of the T-I system responds. The Global-scale Observations of the Limb and Disk (GOLD) mission will determine how the “weather” of the T-I responds, taking the next step in understanding the coupling between the space environment and the Earth’s atmosphere. Operating in geostationary orbit, the GOLD imaging spectrograph will measure the Earth’s emissions from 132 to 162 nm. These measurements will be used image two critical variables—thermospheric temperature and composition, near 160 km—on the dayside disk at half-hour time scales. At night they will be used to image the evolution of the low latitude ionosphere in the same regions that were observed earlier during the day. Due to the geostationary orbit being used the mission observes the same hemisphere repeatedly, allowing the unambiguous separation of spatial and temporal variability over the Americas.
Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other ...psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.
Rapid bifurcations in the plasma response to slowly varying n=2 magnetic fields are observed as the plasma transitions into and out of edge-localized mode (ELM) suppression. The rapid transition to ...ELM suppression is characterized by an increase in the toroidal rotation and a reduction in the electron pressure gradient at the top of the pedestal that reduces the perpendicular electron flow there to near zero. These events occur simultaneously with an increase in the inner-wall magnetic response. These observations are consistent with strong resonant field penetration of n=2 fields at the onset of ELM suppression, based on extended MHD simulations using measured plasma profiles. Spontaneous transitions into (and out of) ELM suppression with a static applied n=2 field indicate competing mechanisms of screening and penetration of resonant fields near threshold conditions. Magnetic measurements reveal evidence for the unlocking and rotation of tearinglike structures as the plasma transitions out of ELM suppression.
A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in ...a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of <1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10(-5), OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies.
ABSTRACT
The BRITICE‐CHRONO Project has generated a suite of recently published radiocarbon ages from deglacial sequences offshore in the Celtic and Irish seas and terrestrial cosmogenic nuclide and ...optically stimulated luminescence ages from adjacent onshore sites. All published data are integrated here with new geochronological data from Wales in a revised Bayesian analysis that enables reconstruction of ice retreat dynamics across the basin. Patterns and changes in the pace of deglaciation are conditioned more by topographic constraints and internal ice dynamics than by external controls. The data indicate a major but rapid and very short‐lived extensive thin ice advance of the Irish Sea Ice Stream (ISIS) more than 300 km south of St George's Channel to a marine calving margin at the shelf break at 25.5 ka; this may have been preceded by extensive ice accumulation plugging the constriction of St George's Channel. The release event between 25 and 26 ka is interpreted to have stimulated fast ice streaming and diverted ice to the west in the northern Irish Sea into the main axis of the marine ISIS away from terrestrial ice terminating in the English Midlands, a process initiating ice stagnation and the formation of an extensive dead ice landscape in the Midlands.
Quantifying gross primary production (GPP) remains a major challenge in global carbon cycle research. Spaceborne monitoring of solar-induced chlorophyll fluorescence (SIF), an integrative ...photosynthetic signal of molecular origin, can assist in terrestrial GPP monitoring. However, the extent to which SIF tracks spatiotemporal variations in GPP remains unresolved. Orbiting Carbon Observatory-2 (OCO-2)'s SIF data acquisition and fine spatial resolution permit direct validation against ground and airborne observations. Empirical orthogonal function analysis shows consistent spatiotemporal correspondence between OCO-2 SIF and GPP globally. A linear SIF-GPP relationship is also obtained at eddy-flux sites covering diverse biomes, setting the stage for future investigations of the robustness of such a relationship across more biomes. Our findings support the central importance of high-quality satellite SIF for studying terrestrial carbon cycle dynamics.
ABSTRACT The total gas mass of a protoplanetary disk is a fundamental, but poorly determined, quantity. A new technique has been demonstrated to assess directly the bulk molecular gas reservoir of ...molecular hydrogen using the HD J = 1-0 line at 112 m. In this work we present a Herschel Space Observatory10 survey of six additional T Tauri disks in the HD line. Line emission is detected at >3 significance in two cases: DM Tau and GM Aur. For the other four disks, we establish upper limits to the line flux. Using detailed disk structure and ray-tracing models, we calculate the temperature structure and dust mass from modeling the observed spectral energy distributions, and we include the effect of UV gas heating to determine the amount of gas required to fit the HD line. The ranges of gas masses are 1.0-4.7 × 10−2 for DM Tau and 2.5-20.4 × 10−2 for GM Aur. These values are larger than those found using CO for GM Aur, while the CO-derived gas mass for DM Tau is consistent with the lower end of our mass range. This suggests a CO chemical depletion from the gas phase of up to a factor of five for DM Tau and up to two orders of magnitude for GM Aur. We discuss how future analysis can narrow the mass ranges further.
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