Heritability of Cardiovascular and Personality Traits in 6,148 Sardinians

In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14–102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old, and in males and females. In summary, we find significant evidence for heritability of many medically important traits, including cardiovascular function and personality. Evidence for heterogeneity by age and sex suggests that models allowing for these differences will be important in mapping quantitative traits

Spectral study of the diffuse synchrotron source in the galaxy cluster Abell 523

The galaxy cluster Abell 523 (A523) hosts an extended diffuse synchrotron source historically classified as a radio halo. Its radio power at 1.4 GHz makes it one of the most significant outliers in the scaling relations between observables derived from multiwavelength observations of galaxy clusters: it has a morphology that is different and offset from the thermal gas, and it has polarized emission at 1.4 GHz typically difficult to observe for this class of sources. A magnetic field fluctuating on large spatial scales (similar to 1 Mpc) can explain these peculiarities but the formation mechanism for this source is not yet completely clear. To investigate its formation mechanism, we present new observations obtained with the LOw Frequency ARray at 120-168 MHz and the Jansky Very Large Array at 1-2 GHz, which allow us to study the spectral index distribution of this source. According to our data the source is observed to be more extended at 144 MHz than previously inferred at 1.4 GHz, with a total size of about 1.8 Mpc and a flux density S-144 MHz = (1.52 +/- 0.31) Jy. The spectral index distribution of the source is patchy with an average spectral index alpha similar to 1.2 between 144 MHz and 1.410 GHz, while an integrated spectral index alpha similar to 2.1 has been obtained between 1.410 and 1.782 GHz. A previously unseen patch of steep spectrum emission is clearly detected at 144 MHz in the south of the cluster. Overall, our findings suggest that we are observing an overlapping of different structures, powered by the turbulence associated with the primary and a possible secondary merger.Peer reviewe

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

The Botanical Record of Archaeobotany Italian Network - BRAIN: a cooperative network, database and website

Con autorización de la revista para autores CSIC[EN] The BRAIN (Botanical Records of Archaeobotany Italian Network) database and network was developed by the cooperation of archaeobotanists working on Italian archaeological sites. Examples of recent research including pollen or other plant remains in analytical and synthetic papers are reported as an exemplar reference list. This paper retraces the main steps of the creation of BRAIN, from the scientific need for the first research cooperation to the website which has a free online access since 2015.Peer reviewe

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies

Flooding scenario for four Italian coastal plains using three relative sea level rise models

The coastal areas of the central Mediterranean Sea are sensitive to climate change and the consequent relative sea level rise. Both phenomena may affect densely urbanized and populated areas, causing severe damages. Our maps show the land-marine flooding projections as effects of the expected relative sea level rise for four Italian coastal plains using (i) IPCC AR5 estimations, based on the IPCC RCP 8.5 emission scenarios and (ii) the Rahmstorf 2007 model. Isostatic and tectonic data were added to the global projections to estimate the relative sea changes expected along the coastline by 2100, as well as sea-flooding. The northern Adriatic map shows the study area, extending for about 5500 km2, and is presented at a scale of 1:300,000 with two inset maps at a scale of 1:150,000. The Oristano coastal plain is about 125 km2; the map scale is at 1:60,000 with an inset map scale at 1:33,000. The Cagliari coastal study area extends for 61 km2; the map scale is at 1:60,000 with two inset maps at 1:30,000. The Taranto area extends for 4.2 km2 and is represented at a scale map of 1:30,000, while the three inset maps are at a scale of 1:10,000

Equilibrative Nucleoside Transporter ENT1 as a Biomarker of Huntington Disease

The initial goal of this study was to investigate alterations in adenosine A2A receptor (A2AR) density or function in a rat model of Huntington disease (HD) with reported insensitivity to an A2AR antagonist. Unsuspected negative results led to the hypothesis of a low striatal adenosine tone and to the search for the mechanisms involved. Extracellular striatal concentrations of adenosine were measured with in vivo microdialysis in two rodent models of early neuropathological stages of HD disease, the Tg51 rat and the zQ175 knock-in mouse. In view of the crucial role of the equilibrative nucleoside transporter (ENT1) in determining extracellular content of adenosine, the binding properties of the ENT1 inhibitor [3H]-S-(4-Nitrobenzyl)-6-thioinosine were evaluated in zQ175 mice and the differential expression and differential coexpression patterns of the ENT1 gene (SLC29A1) were analyzed in a large human cohort of HD disease and controls. Extracellular striatal levels of adenosine were significantly lower in both animal models as compared with control littermates and striatal ENT1 binding sites were significantly upregulated in zQ175 mice. ENT1 transcript was significantly upregulated in HD disease patients at an early neuropathological severity stage, but not those with a higher severity stage, relative to non-demented controls. ENT1 transcript was differentially coexpressed (gained correlations) with several other genes in HD disease subjects compared to the control group. The present study demonstrates that ENT1 and adenosine constitute biomarkers of the initial stages of neurodegeneration in HD disease and also predicts that ENT1 could constitute a new therapeutic target to delay the progression of the disease