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Background: The Worm Study, ascertained from a multigeneration pedigree segregating a single amino acid deletion in SCN5A (c.4850_4852delTCT, p.(Phe1617del), rs749697698), is characterized by substantial phenotypic heterogeneity and overlap of sudden cardiac death, long-QT syndrome, cardiac conduction disease, Brugada syndrome, and isorhythmic atrioventricular dissociation. Linkage analysis for a synthetic trait derived from these phenotypes identified a single peak (logarithm of the odds [LOD] = 4.52) at the SCN5A/SCN10A/SCN11A locus on chromosome 3. Objective: This study explored the role of additional genetic variation in the chromosome 3 locus as a source of phenotypic heterogeneity in the Worm Study population. Methods: Genotypes underlying the linkage peak (n = 70) were characterized using microarrays. Haplotypes were determined using family-aware phasing and a population-specific reference panel. Variants with minor allele frequencies >0.10 were tested for association with cardiac conduction disease and isorhythmic dissociation using LAMP and logistic regression. Results: Only 1 haplotype carried the p.Phe1617del/rs749697698 deletion, suggesting relatively recent development (∼18 generations); this haplotype contained 5 other missense variants spanning SCN5A/SCN10A/SCN11A. Noncarrier haplotypes (n = 74) ranged in frequency from 0.5% to 5%. Although no variants were associated with cardiac conduction disease, a homozygous missense variant in SCN10A was associated with isorhythmic dissociation after correction for multiple comparisons (odds ratio 11.23; 95% confidence interval 2.76–23.39; P = 1.2 × 10 −4). This variant (rs12632942) was previously associated with PR interval. Conclusion: Our data suggest that other variants, alongside a pathogenic mutation, are associated with phenotypic heterogeneity. Single-mutation screening may be insufficient to predict electrical heart disease in patients and family members. In the Worm Study population, segregating a pathogenic SCN5A mutation, compound variation in the SCN5A/SCN10A/SCN11A locus determines arrhythmic outcome.

The article sets the timeframe for the main phenological stages of peach, as well as the required amount of effective temperatures above +5 °C for their passing and growing season length based on the example of the variety of Belarusian selection Loiko. The terms of the beginning of an organogenesis of flower rudiments after a severe winter and damage of generative buds, skeletal branches are outlined. The peculiarities of the differentiation process during the growing season and the required amounts of effective temperatures for each stage of flower organogenesis in the central zone of Belarus are presented. The data obtained show that in late November the process of differentiation in most generative buds stops at stage VII b with a well-defined rudiment of the pistil and its clear differentiation into stigma and style. In the case of thawing during the winter, the process of organogenesis does not stop, and in February the development of flower buds in the generative buds reaches stage VIII with the formation of the ovary and the growth of stamens with anthers of characteristic shape.

The paper is devoted to the representation of Protestants in the stories (legends and miracles) about the miraculous images of Our Lady that come from the territories of the (former) Grand Duchy of Lithuania: involving those currently incorporated in Belarus, Lithuania, Poland and Ukraine. It considers first the representation of both the locals who converted to Protestantism from Orthodoxy or Catholicism in the 16th–17th century and the Lutheran Swedish invaders of the 17th–18th century by their contemporaries and later investigates into how the image of Protestants changed with the course of time up to nowadays and what had an impact on this. Interestingly, that since the 19th century military invaders from Sweden were described in interchangeable manner with the French soldiers of Napoleon Bonaparte’s troops. And now we are witnessing the genesis of a German Nazi soldiers presentation in the miracles attributed to Virgin Mary’s images/icons.

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.

The article is devoted to the miraculous icon of Our Lady of Novy Dvor, which was located in the Orthodox Monastery in Novy Dvor (Belarus, Brest Oblast) from the 17th until the first half of the 18th century. It considers the iconography of the icon based on two engravings by Jan (Ivan) Szczyrski. On one of them, next to the image of Mary and Child there is an inscription in the Church-Slavonic language and on the other – in Latin. The article contains a description of the icon and votives based on an inventory of 1719. It also considers legends associated with the icon and the time when the icon was salvaged from Novy Dvor., Artykuł jest poświęcony cudownej ikonie Matki Bożej Nowodworskiej, która w XVII w. i w pierwszej połowie XVIII w. znajdowała się w prawosławnym monasterze w Nowym Dworze koło Pińska (Białoruś, obwód brzeski). Analizie poddano ikonografię ikony na podstawie dwóch rycin autorstwa Jana Szczyrskiego. Na jednej z nich obok wizerunku Marii z Dzieciątkiem widoczny jest napis w języku cerkiewnosłowiańskim, a na drugiej – łacińskim. Przytoczono opis cudownej ikony i zawieszek wotywnych zawarty w wizytacji cerkwi z roku 1719, jak również związane z nią legendy. Omówiono kwestię czasu wywiezienia ikony z Nowego Dworu.

Objectives Observational analyses suggest that high bone mineral density (BMD) is a risk factor for osteoarthritis (OA); it is unclear whether this represents a causal effect or shared aetiology and whether these relationships are body mass index (BMI)-independent. We performed bidirectional Mendelian randomization (MR) to uncover the causal pathways between BMD, BMI and OA. Methods One-sample (1S)MR estimates were generated by two-stage least-squares regression. Unweighted allele scores instrumented each exposure. Two-sample (2S)MR estimates were generated using inverse-variance weighted random-effects meta-analysis. Multivariable MR (MVMR), including BMD and BMI instruments in the same model, determined the BMI-independent causal pathway from BMD to OA. Latent causal variable (LCV) analysis, using weight-adjusted femoral neck (FN)–BMD and hip/knee OA summary statistics, determined whether genetic correlation explained the causal effect of BMD on OA. Results 1SMR provided strong evidence for a causal effect of BMD estimated from heel ultrasound (eBMD) on hip and knee OA {odds ratio [OR]hip = 1.28 [95% confidence interval (CI) = 1.05, 1.57], p = 0.02, ORknee = 1.40 [95% CI = 1.20, 1.63], p = 3 × 10–5, OR per standard deviation [SD] increase}. 2SMR effect sizes were consistent in direction. Results suggested that the causal pathways between eBMD and OA were bidirectional (βhip = 1.10 [95% CI = 0.36, 1.84], p = 0.003, βknee = 4.16 [95% CI = 2.74, 5.57], p = 8 × 10–9, β = SD increase per doubling in risk). MVMR identified a BMI-independent causal pathway between eBMD and hip/knee OA. LCV suggested that genetic correlation (i.e. shared genetic aetiology) did not fully explain the causal effects of BMD on hip/knee OA. Conclusions These results provide evidence for a BMI-independent causal effect of eBMD on OA. Despite evidence of bidirectional effects, the effect of BMD on OA did not appear to be fully explained by shared genetic aetiology, suggesting a direct action of bone on joint deterioration.

The article is devoted to the icon of Our Lady of Lady from the Basilian monastery in Malyia Lady located not far from Minsk (Belarus). The cult of the icon was local and existed from the first half of the 18th century till the first half of the 20th century. The icon was a copy of the icon of Our Lady of Žyrovicy and its cult was closely related to that of the icon of Our Lady of Žyrovicy that strengthened after the coronation in 1730 and occasional discovery of its copy in the Santi Sergio e Bacco church in Rome during the renovation in 1718. These both motives were reflected in the history of icon from Lady. The earliest legendary reference on the origin of the icon cult are contained in two poems dating back to 1744 which have preserved in a hand-written set of religious texts and attached to the article.

The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome sequencing (WGS) in 1328 individuals. We discover 131 independent sequence variant associations (P, The human proteome represents a crucial link between complex disease and genetic/environmental factors. Here, the authors investigate 257 cardiometabolic-relevant protein biomarkers in whole genome sequencing data from 1328 individuals, revealing the genetic architecture underlying biomarker variation.

Heart rate variability (HRV) is understood as the severity of fluctuations in heart rate or RR-intervals in relation to their average values. HRV is defined as the actual variability of the duration of the RR-intervals between consistent heart contraction cycles for a certain period of time. Traditional methods for analyzing heart rate variability are often insufficient to characterize the complex heartbeat dynamics, since the mechanisms involved in the regulation of the cardiovascular system are likely to interact with each other in a non-linear manner. The article represents data on the association between non-linear parameters of heart rate variability in patients with cardiovascular diseases. It can be concluded, that the non-linear analysis of HRV provides useful information for characterizing the autonomic balance and is a reliable marker of complications and mortality in patients with cardiovascular diseases.

Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356; 22.5× WGS) and Pomak (n = 1537; 18.4× WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes. © 2022, The Author(s).

Despite the increasing global burden of neurological disorders, there is a lack of effective diagnostic and therapeutic biomarkers. Proteins are often dysregulated in disease and have a strong genetic component. Here, we carry out a protein quantitative trait locus analysis of 184 neurologically-relevant proteins, using whole genome sequencing data from two isolated population-based cohorts (N = 2893). In doing so, we elucidate the genetic landscape of the circulating proteome and its connection to neurological disorders. We detect 214 independently-associated variants for 107 proteins, the majority of which (76%) are cis-acting, including 114 variants that have not been previously identified. Using two-sample Mendelian randomisation, we identify causal associations between serum CD33 and Alzheimer’s disease, GPNMB and Parkinson’s disease, and MSR1 and schizophrenia, describing their clinical potential and highlighting drug repurposing opportunities., Serum proteins are easily accessible biomarkers and drug targets. Here, the authors use whole genome sequencing data to describe the genetic architecture of neurologically-relevant serum proteins and establish causal protein-neurological disease relationships.

Background In recent decades, a significant number of epidemiological studies showed the association between asymptomatic hyperuricemia and development of arterial hypertension (HTN) and atrial fibrillation (AF). The key enzyme participating in disintegration purines to uric acid is xanthine oxidase (XO). The accumulated data suggest the existence of a direct pathophysiological role of increased level of serum uric acid (SUA) and XO activity with a risk of HTN and AF. Purpose To evaluate the features of disorders of UA metabolism in patients with HTN and AF. Materials and methods The study included male patients 27 to 65 years, with a body mass index (BMI) less than 30 kg/m2 and more than 18.5 kg/m2. All patients were investigated of the level of a SUA, hypoxanthine/xanthine, inosine/adenosine, XO enzyme activity. Depending on the presence of AF, all patients were divided into 2 groups: group 1 (n=16) patients with HTN, group 2 (n=16) patients with HTN and AF. Results Table 1 shows the indicators of purine metabolism in the compared groups. The analysis of the results demonstrates that in group 1 the smallest level of a SUA in comparison with group 2 (0.35 [0.31; 0.41] vs 0.41 [0.39; 0.40](μmol/l), p=0.003), hypoxanthine 3.02 [1.80; 5.63] vs 7.35 [4.56; 8.25](μmol/l), p=0.008; inosine 1.59 [1.25; 4.48] vs 7.41 [1.49; 17.24](μmol/l), p=0.002. An increase level of a SUA is noted in 31.2% of patients from group 1 (5 patients out of 16) and 68.7% of patients from group 2 (11 patients out of 16). As a result of Spearman's correlation analysis in the group of patients with HTN and AF, a direct correlation was found between the experience of AF and BMI (r=0.681), SBP (r=0.487); level of hypoxanthine and inosine (r=0.808) and the inverse correlation between the level of xanthine and inosine (r=−0.547), as well as the association between the level of XO and SUA (r=0.796), XO and BMI (r=0.812). In the group of patients with HTN was determined association between the level of hypoxanthine and inosine (r=0.604), xanthine and adenosine (r=0.539), inosine and adenosine (r=0.657), a direct association between the level of XO and adenosine (r=0.642), inosine (r=0.502), BMI (r=0.791). Conclusions As a result of the study of patients with isolated HTN in combination with AF at the age of 27 to 65 years and a BMI of less than 30 kg/m2 and more than 18.5 kg/m2, an increase level of SUA and intermediate metabolites of UA synthesis such as inosine and hypoxanthine is observed compared with group with isolated HTN. An increase in level of XO is associated with an increase level of SUA and BMI. In the group of patients with HTN, an increase in level of inosine is associated with an increase level of hypoxanthine, but an increased level of inosine is associated with a decrease in level of xanthine. The XO level in this group is associated with an increase in level of adenosine and inosine, BMI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Grodno State Medical University, Grodno, Belarus Table 1. Comparative characteristics of indicators in groups 1 and 2