52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.This work was supported by a grant from the US National Heart, Lung, and Blood Institute (N01-HL-25195; R01HL 093328 to RSV), a MAIFOR grant from the University Medical Center Mainz, Germany (to PSW), the Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, and the Federal Ministry of Research and Education, Germany (BMBF 01EO1003 to PSW). This work was also supported by the research project Greifswald Approach to Individualized Medicine (GANI_MED). GANI_MED was funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania (contract 03IS2061A). We thank all study participants, and the colleagues and coworkers from all cohorts and sites who were involved in the generation of data or in the analysis. We especially thank Andrew Johnson (FHS) for generation of the gene annotation database used for analysis. We thank the German Center for Cardiovascular Research (DZHK e.V.) for supporting the analysis and publication of this project. RSV is a member of the Scientific Advisory Board of the DZHK. Data on CAD and MI were contributed by CARDIoGRAMplusC4D investigators. See Supplemental Acknowledgments for consortium details. PSW, JFF, AS, AT, TZ, RSV, and MD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

Diari spagnoli di Nizar Qibbani

Diari spagnoli di Nizar Qabbani. Traduzione dall'arabo all'italiano delle poesie: Ricordi dell'Andalusia, Granada, Le carte spagnol

Volunteering and self-assessed health in the EWC Survey within EU 12

Studio delle determinanti della salute percepita ed effetto delle attività di volontariat

Perceived stress across EU countries: does working from home impact?

The study concerns the relationship between self-assessed work related stress and the main characteristics of workers as observed in the 6th European Working Conditions Survey. The analysis, carried out by means of a heteroskedastic Ordered Probit model, highlights results partially expected, such as the effect of gender on the response pattern and the influence of the presence of children, but also unexpected findings such as the statistical non-significance of certain family care commitments. Future research will be directed at investigating the role of gender and the distinction between employees and the self-employed respondents

Lo stress da lavoro: uno studio sulla base della European Working Conditions Survey 2015

abstract non presente per motivi editorial

Volunteering and self-assessed health within EU28: evidence from the 6th European Working Conditions Survey

Volunteering is remarkably widespread in almost all the European countries and the number of people involved has been growing over time. In recent years, some scholars stimulated an interesting discussion to assess whether volunteering exerts beneficial effects also for the volunteers themselves. It is well known that people who volunteer are likely to gain work experience, raising their future employability (when unemployed) and earning power (when employed). Moreover, some empirical studies show the presence of a wage premium for volunteers. Studies that validate the health benefits of volunteering are numerous, so that non-profit organizations started using them to highlight such results in volunteers' recruitment campaigns. The paper aims at detecting the effects of volunteering (and those of other free and philanthropic activities) on self-perceived health, using data stemming from the Sixth European Working Conditions Survey, carried out in 2015, which provides a wide-ranging picture of Europe at work, across countries, occupations, sectors and age groups. Our analysis is focused on workers' responses to investigate whether the ones who volunteer report a better self-assessed health, highlighting the effects of some specific drivers. Since this kind of qualitative variables are naturally ordered, we implemented an ordered probit model

Volunteering and Self-Assessed Health Within EU28 Countries: Evidence From the EWCS

The effects of voluntary activities on individual well-being have been investigated extensively in the literature. In this study, the relationship between self-assessed health and volunteering is examined from a cross-country perspective by considering respondents’ characteristics and other voluntary liabilities, employing the Sixth European Working Conditions Survey. This data set allows us to explore, by implementing an Ordered Probit model, the association of self-assessed health status with charity activities performed specifically by workers. Among the working population in the European Union, our results show that, although volunteering—as well as other unpaid tasks, such as informal helping—are statistically significant, voluntary activities do not seem to be strongly associated with individual perceived health status

ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies

The development of the B-lymphoid cell lineage is tightly controlled by the concerted action of a network of transcriptional and epigenetic regulators. EBF1, a central component of this network, is essential for B-lymphoid specification and commitment as well as for the maintenance of the B-cell identity. Genetic alterations causing loss of function of these B-lymphopoiesis regulators have been implicated in the pathogenesis of B-lymphoid malignancies, with particular regard to B-cell acute lymphoblastic leukaemias (B-ALLs), where their presence is frequently detected. The activity of the B-cell regulatory network may also be disrupted by the aberrant expression of inhibitory molecules. In particular, two multi-zinc finger transcription cofactors named ZNF423 and ZNF521 have been characterised as potent inhibitors of EBF1 and are emerging as potentially relevant contributors to the development of B-cell leukaemias. Here we will briefly review the current knowledge of these factors and discuss the importance of their functional cross talk with EBF1 in the development of B-cell malignancies