Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Development of Models for the Formalized Description of Modular E-learning Systems for the Problems on Providing Ergonomic Quality of Human-computer Interaction

A complex of the systems models of e-learning, necessary for the provision of ergonomic quality, was developed. Relevance of this development is determined by a wide propagation of electronic learning technologies and insufficient level of their effectiveness, which is mainly defined by the existence of means of ergonomic quality management. It was established that, if we describe software and hardware learning means, electronic learning modules, humans-operators, means of ergonomic provision, implied in the system of dialogue interaction technology relying on a totality of component and morphological structures, it will be possible to formulate requirements for the system of e-learning data and knowledge bases.A standard structure of component and morphological models for e-learning was formed. It was shown that the application of such models provides the e-learning adaptive capacity, and as a consequence, higher quality of human-computer interaction. The development may be useful for the formation of systems of information support of e-learning and provide essential enhancement of working conditions and motivation of people, trained in information learning environments of secondary educational institutions, universities, enterprises, firms, etc

Development of A Method for Assessing Forecast of Social Impact in Regional Communities

The development of the social aspect of the world community is closely related to the expansion of the range of digital services in cyberspace. A special place in which social networks occupy. The world's leading states are conducting information operations in this environment to achieve geopolitical goals. Such processes are reflected in real social and political life. This makes it possible to influence not only the social groups of society, but also to ensure manipulation in political "games" in the conduct of hybrid wars. The simultaneous interaction of social factors, influencing factors, the presence of communities in social networks forms a full-fledged socio-cyber-physical system capable of integrating real and virtual interactions to manage regional communities. The article proposes a method for predicting the assessment of social mutual influence between “formal” and “informal” leaders and regional societies. The proposed models make it possible to form not only a forecast of the influence of agents, but also the interaction of various agents, taking into account their formal and informal influences, the use of administrative resources, political moods of the regional society. This approach allows dynamic modeling based on impact and relationship analysis. The presented results of simulation modeling do not contradict the results of opinion polls and make it possible to form a set of measures that can be aimed at overcoming the negative impact on the regional society of both individual “leaders” and political parties. Analysis of the simulation results allows to increase both the political and social stability of the regional society, helps to prevent conflict moods and contradictions

Development of the Space-time Structure of the Methodology for Modeling the Behavior of Antagonistic Agents of the Security System

The rapid development of computer technology, the emergence of modern cyber threats with signs of hybridity and synergy put forward strict requirements for the economic component of national security and especially the processes of ensuring the economy cybersecurity. The cybersecurity industry is trying to meet today's requirements by introducing new and more advanced security technologies and methods, but it is believed that such a universal approach is not enough. The study is devoted to resolving the objective contradiction between the growing practical requirements for an appropriate level of cybersecurity of business process contours while increasing the number and technological complexity of cybersecurity threats. Also the fact that threats acquire hybrid features on the one hand, and imperfection, and sometimes the lack of methodology for modeling the behavior of interacting agents of security systems should be taken into account. However, this does not allow timely prediction of future actions of attackers, and as a result, determining the required level of investment in security, which will provide the required level of cybersecurity.The paper proposes the Concept of modeling the behavior of interacting agents, the basis of which is a three-level structure of modeling the subjects and business processes of the contours of the organization and security system, based on modeling the behavior of antagonistic agents. The proposed methodology for modeling the behavior of interacting agents, which is based on the Concept of behavior of antagonistic agents, allows assessing and increasing the current level of security by reducing the number of hybrid threats by 1.76 times, which reduces losses by 1.65 times and increases the time for choosing threat counteraction means by reducing the time to identify threats online by 38

Genome-wide physical activity interactions in adiposity:a meta-analysis of 200,452 adults

Abstract Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery

Exome-wide association study of plasma lipids in >300,000 individuals.

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p