Importance:Elevated intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma, and genetic risk scores hold promise as a tool for screening for ocular hypertension. However, genetic risk scores for IOP have a nonuniform association across the range of IOP, which reduces their accuracy. Objective:To test the hypothesis that nonuniform behavior of genetic risk scores for IOP is associated with a specific type of genetic interaction. Design, Setting, and Participants:Cross-sectional, post hoc genetic association studies were performed using linear and quantile regression in a sample of UK Biobank participants. Data were analyzed from January to September 2025. Exposures:Ninety-eight genetic variants associated with IOP. Main Outcomes and Measures:Tests were carried out for 98 genetic variants associated with IOP (P < 5.0 ×10-8) to examine (1) dominant or recessive genetic effects, (2) genotype × genotype interactions, (3) genotype × age interactions, and (4) genotype × sex interactions. Results:A total of 98 235 participants (mean [SD] age, 58.1 [7.9] years; 52 168 female [53.1%]) were included in this analysis. More variants exhibited genotype × age interactions than expected by chance (14 of the 98 variants associated with IOP had at least nominal evidence of an interaction with age; P = 3.76 ×10-4). For 12 of these 14 variants, age increased rather than decreased the magnitude of the IOP vs genotype association. However, integrating age interactions into the genetic risk score construction process did not yield improved accuracy (incremental noninteraction model, R2 = 4.05; 95% CI, 3.82-4.31 and interaction model, R2 = 4.04; 95% CI, 3.80-4.27). There was little support for other types of genetic interaction. Conclusions and Relevance:In the current work, findings show minimal evidence that nonadditive allelic effects, genotype × genotype interactions, and genotype × sex interactions contributed to the nonuniform association of genetic variants with IOP across quantiles of IOP. Although a genetic risk score for IOP was more accurate in older vs younger individuals, efforts to account for genotype × age interactions in genetic risk score construction did not improve accuracy. These findings suggest other factors, such as gene-environment interactions, contribute to the nonuniform relationship of genetic variants with IOP.

Strabismus is a common pediatric eye misalignment and has complex genetic and environmental causes. Previous genome-wide association studies (GWAS) encountered difficulties in identifying strabismus risk variants due to heterogeneity and small samples. We performed large meta-analyses of 11 European-ancestry GWAS (7 sources), analysing broad strabismus (20,464 cases, 954,921 controls) and subtypes (esotropia/exotropia). We discovered 4 loci (e.g., NPLOC4-TSPAN10-PDE6G-FAAP100, COL6A1) for strabismus and 5 additional loci (e.g., CHRNA4, MAD1L1) for strabismus subtypes and we successfully replicated the previously reported strabismus variant near NPLOC4-TSPAN10-PDE6G-FAAP100. Using mendelian randomisation, we found genetic evidence supporting maternal smoking as a causal risk factor for strabismus in offspring.

In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBGcon) and uterine fibroids (UFs). The work was performed on a sample of 1542 women (569 with UFs and 973 without UFs [control]), from whom we obtained experimental data on the distribution of nine single-nucleotide polymorphisms (SNPs) affecting the SHBGcon (data confirmed in genome-wide association studies [GWASs]). When searching for associations with UFs, both the independent effects of SNPs and the effects of their SNP–SNP interactions (SNP-SNPints) were taken into account during the “deep study” of the functionality of seven important UF loci and 115 strongly linked [r2 ≥ 0.80] variants (an in silico methodology was used). As the results show, two SHBGcon-related SNPs correlated with UF risk: rs3779195 [T/A] BAIAP2L1 (ORAA = 0.38; 95%CIAA = 0.20–0.91; pperm(AA) = 0.023) and rs440837 [A/G] ZBTB10 (ORGG = 1.93; 95%CIGG = 1.17–3.14; pperm(GG) = 0.010). At the same time, seven SHBGcon-related SNPs interacting with each other (four models of such SNP-SNPints [pperm ≤ 0.01)] were found to influence UF risk. These SHBGcon-related SNPs, determining susceptibility to UF, showed strong functional relevance and were involved in pathways of gene transcription regulation, interactions with hormone ligand-binding receptors, the content control of SHBG, testosterone, liver enzymes, lipids, etc. This study’s results demonstrate the effect of significant SHBGcon-related genetic determinants of UF risk.

Abstract Importance: Glaucoma is one of the world's leading causes of irreversible blindness and effective interventions with less side effect and less cost were still in need. Objective: To investigate the potential of repurposing antihypertensive drugs to glaucoma treatment and intra ocular pressure (IOP) lowering in cost effective manners. Design, Setting and Participants: Two sample Mendelian Randomization (MR) was used to investigate the genetic effect of antihypertensive drugs on glaucoma protection or IOP lowering. Two strategies (biomarker or eQTL approach) were applied to define the instrumental variable (IV). Genome wide association study (GWAS) results on systolic blood pressure (SBP) of 526,001 European participants were used as exposure and GWAS on primary open angle glaucoma (POAG, 15,229 cases and 177,473 controls) and on IOP compromising 70832 participants in the UK Biobank were used as the outcome. All analyses were performed between April 2022 and December 2022. Exposures: The SBP lowering effect of the antihypertensive drug targets. Main Outcomes and Measures: POAG or IOP measurements. Results: Using IVs defined by the biomarker approach, genetically proxied lower SBP through diuretics targets was causally associated with a reduced risk of glaucoma (OR per mmHg reduction in SBP 0.87, 95% CI: 0.97 to 0.78, P = 0.009 for potassium sparing diuretics [PSD] and OR=0.86, 95% CI: 0.92 to 0.81,P=2.67e-05 for loop diuretics [LD]). When using eQTL as IVs, the IVW MR yielded a causal effect estimate on POAG of 0.88 (95% CI 0.79 to 0.97, P = 0.011) per 1 mmHg decrease in blood pressure via PSD targets and 0.92 (95% CI 0.85 to 1, P = 0.052) via LD. No consistence effects were observed among different MR methods for other antihypertensive drugs on glaucoma or IOP. After triangulation genetic evidence from MR, epidemiological evidence from observational studies and experimental evidence, the protective effect of PSD/LD on POAG was suggested. Conclusions and Relevance: We found PSD and LD drugs hold promise as potential therapeutic agents to reduce the risk of POAG ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement HY receives support from the NSFC Young Scientist Found (82301246); Research Foundation of Medical Science and Technology of Guangdong Province, China (A2022323); NSFC Incubation Project of Guangdong Provincial People's Hospital, China (KY0120220051) and Science and Technology Program of Guangzhou, China (202002020049); DP was supported by a grant from Kazan State Medical University (2/22-2 01.08.2022); ZZ receives support from the National Natural Science Foundation of China (81870663, 82171075), the Outstanding Young Talent Trainee Program of Guangdong Provincial People's Hospital (KJ012019087), Guangdong Provincial People's Hospital Scientific Research Funds for Leading Medical Talents and Distinguished Young Scholars in Guangdong Province (KJ012019457), Talent Introduction Fund of Guangdong Provincial People's Hospital (Y012018145). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: For UK Biobank participants, ethical approval was obtained from the National Health Research Ethics Service (Reference 11/NW/0382), and all participants provided (digital) written informed consent. The study adhered to the tenets of the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Background: Neck pain is one of the most prevalent musculoskeletal complaints and has recently been recognized as a frequent comorbidity of osteoarthritis (OA). Whether this association reflects shared biological mechanisms or bidirectional influences remains unclear. Objectives: To investigate the bidirectional associations between genetic liability to neck pain and OA at three major joint sites (knee, hand, and hip) using Mendelian randomization (MR). Methods: A two-sample bidirectional MR study was conducted using summary-level data from large genome-wide association studies of neck pain (579,152 participants from the Million Veteran Program) and of knee, hand, and hip OA (up to 1.3 million participants from the international Osteoarthritis Consortium). The primary analysis was random-effects inverse-variance weighted (IVW). The additional analyses comprised of multiple pleiotropy-robust sensitivity methods (weighted median, mode-based estimators, MR-Egger, MR-PRESSO, MR-Lasso). Results: Genetic liability to neck pain was positively associated with knee OA (IVW OR = 1.24, 95 % CI 1.10-1.41, p < 0.001) and showed a weaker, non-significant association with hand OA after correction for multiple testing (OR = 1.41, 95 % CI 1.03-1.95, p = 0.031). No association was observed with hip OA. In the reverse direction, genetic liability to knee (OR = 1.07, 95 % CI 1.03-1.11, p < 0.001) and hip OA (OR = 1.05, 95 % CI 1.02-1.07, p < 0.001) were associated with increased risk of neck pain, whereas hand OA showed no effect. Sensitivity analyses yielded consistent results with no evidence of directional pleiotropy. Conclusions: Genetic predisposition to neck pain was associated with a higher risk of knee OA, while genetic predisposition to knee and hip OA was associated with higher risk of neck pain. These bidirectional associations suggest overlapping biological pathways that warrant confirmation in independent studies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was carried out within the regular institutional research program of the Research Institute of Internal and Preventive Medicine (project FWNR-2024-0002) and received no separate funding beyond the author's regular salary. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No individual-level data were accessed or used in this analysis. All data used in this study were obtained from publicly available GWAS summary statistics.GWAS summary statistics for neck pain were obtained from the U.S. Department of Veterans Affairs Million Veteran Program and are accessible through the GWAS Catalog under accession GCST90480571 (https://www.ebi.ac.uk/gwas/studies/GCST90480571). GWAS summary statistics for knee, hand, and hip osteoarthritis (OA) were obtained from the international Osteoarthritis Consortium and are available through the GWAS Catalog under accessions GCST90566800 (https://www.ebi.ac.uk/gwas/studies/GCST90566800), GCST90566797 (https://www.ebi.ac.uk/gwas/studies/GCST90566797), and GCST90566798 (https://www.ebi.ac.uk/gwas/studies/GCST90566798), respectively. The custom scripts contain institution-specific file paths and are available from the corresponding author upon reasonable request. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes No individual-level data were accessed or used in this analysis. All data used in this study were obtained from publicly available GWAS summary statistics.GWAS summary statistics for neck pain were obtained from the U.S. Department of Veterans Affairs Million Veteran Program and are accessible through the GWAS Catalog under accession GCST90480571 (https://www.ebi.ac.uk/gwas/studies/GCST90480571). GWAS summary statistics for knee, hand, and hip osteoarthritis (OA) were obtained from the international Osteoarthritis Consortium and are available through the GWAS Catalog under accessions GCST90566800 (https://www.ebi.ac.uk/gwas/studies/GCST90566800), GCST90566797 (https://www.ebi.ac.uk/gwas/studies/GCST90566797), and GCST90566798 (https://www.ebi.ac.uk/gwas/studies/GCST90566798), respectively. The custom scripts contain institution-specific file paths and are available from the corresponding author upon reasonable request.

Introduction To investigate the association of genetically predicted migraine with the risk of primary open-angle glaucoma (POAG). Methods To estimate the shared genetic basis of migraine and POAG, we conducted genome-wide genetic correlation analyses using cross-trait linkage disequilibrium score regression. To assess potential causal effects of migraine on POAG risk, we conducted two-sample Mendelian randomization (MR) analyses using data from European ancestry individuals. Genetic instruments (N = 54 genetic variants with minor allele frequency (MAF) ≥ 0.01) were derived from our previous genome-wide association study (GWAS) of migraine conducted in the UK Biobank (16,709 migraine cases and 438,178 controls). For POAG, we used GWAS summary statistics from our previous GWAS conducted in the GERA cohort (3836 POAG cases and 48,065 controls) or using data from the International Glaucoma Genetics Consortium (15,229 POAG cases and 177,473 controls). The inverse-variance weighted (IVW) method was our primary source of MR estimates and common sensitivity analyses were conducted. Results We found that migraine was not genetically associated with POAG ( r g = 0.05; SE = 0.11; P = 0.69). Further, we did not detect any evidence of association between genetically predicted migraine with POAG. Conclusion Our results provide evidence that genetic risk for migraine may not be a strong causal risk factor for POAG.

Introduction . In Tomsk Region specialized medical care for the patients with acute cerebrovascular disorders has been provided and coordinated since 2012 by the Regional Vascular Center of Tomsk Regional Clinical Hospital where more than three-quarters of all stroke patients in the region are admitted annually. Aim : To study the dynamics of mortality rates in different nosological forms of stroke, gender and age characteristics of the patients who died from stroke, the example of the work of the Regional Vascular Center of Tomsk Regional Clinical Hospital being used, and to determine the directions for further improvement of medical care organization. Materials and Methods. At the first stage, the assessment of the dynamics of mortality rates from different nosological forms of stroke in Tomsk Regional Clinical Hospital according to the Federal Statistical Observation Form No. 14 from 2018 to 2022 was performed. At the second stage of the study, based on data from registration form No. 066/u of the Regional Vascular Center, the structure of gender and age of the patients who died from stroke was analyzed, the average age of death of the patients with stroke, their gender and age characteristics, taking into account the form of stroke, were determined. Results . Mortality rates from stroke in Tomsk Regional Clinical Hospital were relatively stable and quite high – 23.6–24.8%; the greatest fluctuations in mortality rates (36.0–59.6%) and (46.7–56.9%) were observed in hemorrhagic forms. The average age of death from stroke in men at the Regional Vascular Center was 12 years lower than in women – 67.0 (59.0–76.0) years. Distinct gender differences were revealed among deceased patients with a significant predominance of men – 73.0 and 68.6% in the age groups 18–44 years and 45–59 years. Conclusion . Directions for further improvement of medical care organization have been identified: opening an additional vascular center, developing mechanisms for timely re-evacuation of patients, optimizing the system for managing stroke risk factors.

Introduction. Bridging therapy is the main method of treating ischemic stroke (IS) due to proximal occlusion, the effectiveness of which depends on the speed of its implementation. It is possible to increase the speed of systemic thrombolytic therapy (STT) and reduce the delay before mechanical thrombectomy (MT) by using bolus forms of thrombolytic drugs.Aim. To evaluate the efficacy and safety of using non-immunogenic staphylokinase compared to alteplase in bridging therapy of IS in real clinical practice of a regional stroke center (RSC).Materials and methods. A retrospective study of the combined use of STT and MT for the treatment of IS due to proximal occlusion was conducted from the reperfusion therapy registry of the RSC of the Tomsk Regional Clinical Hospital from 2017 to 2023. The final analysis included 49 patients who received non-immunogenic staphylokinase and 26 patients who received alteplase.Results. The time between the stages of bridging therapy was 92.0 [65.0–130.0] min in the non-immunogenic staphylokinase group and 35.0 [25.0–50.0] min in the alteplase group (p < 0.001). No intergroup differences were found in the incidence of symptomatic hemorrhagic transformation: 8.1% in the non-immunogenic staphylokinase group and 3.8% in the alteplase group (p = 0.476). Mortality in both groups did not differ significantly and was 30.6% and 26.9%, respectively. Favorable functional outcome was observed in 40.8% of patients in the non-immunogenic staphylokinase group and in 23.1% in the alteplase group (p = 0.151).Conclusion. Comparable efficacy and safety of non-immunogenic staphylokinase and alteplase in the context of staged reperfusion therapy were revealed. The use of non-immunogenic staphylokinase is associated with a decrease in the time between the stages of bridging therapy.

The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma. The mechanisms connecting intraocular pressure to glaucoma remain unclear. Here, the authors use GWAS by subtraction to reveal intraocular pressure-independent aspects of glaucoma.

Purpose: Primary open-angle glaucoma (POAG) represents the most prevalent form of glaucoma and stands as a foremost contributor to irreversible vision impairment on a global scale. Despite notable strides made in comprehending the genetic underpinnings of POAG, investigations within the context of Russia remain constrained.Methods: The study cohort comprised a total of 235 individuals, with 135 of them exhibiting various forms of glaucoma encompassing both POAG and (NTG, while the remaining 100 individuals served as control subjects. Each participant underwent a comprehensive ocular examination to ascertain their ocular health status. Genotyping of the relevant single nucleotide polymorphisms (SNPs) was carried out using the Taq Man genotyping assay. Specifically, the two SNPs under scrutiny were GNB3 rs5443 gene and ACE rs4646994. Statistical analysis was performed to evaluate the association of these SNPs with glaucoma risk.Results: The presence of the T allele of rs5443 was found to be associated with NTG (p = .004). However, no statistically significant correlation was identified between this SNP and POAG (p = .88).Conclusion: This study provides evidence of an association between the T allele of rs5443 and a reduced susceptibility NTG within the Russian population. These observations augment the comprehension of the genetic underpinnings of glaucoma and hold potential implications for the prospective development of targeted therapeutic interventions.

OBJECTIVE To study the dynamics of population indicators: the total number of deaths from diseases of the circulatory system, coronary heart disease, cerebrovascular diseases and strokes, hospitalization profile for strokes, their structure and mortality in the Tomsk region for several years in comparison with these indicators for the Russian Federation and the Siberian Federal District. MATERIAL AND METHODS A retrospective study was conducted using acute cerebrovascular accidents monitoring data and data of the Territorial body of state statistics of the Tomsk region in comparison with the literature data. The indicators of all causes of death, from circulatory diseases, coronary heart disease, cerebrovascular diseases and stroke in the territory of the Tomsk region, profile of hospitalization, structure of acute cerebrovascular accidents were analyzed for several years. Particular attention was paid to case fatality rate, one of the key indicators of the effectiveness of the system of care for patients with stroke. RESULTS Typical for many regions of the Russian Federation predominance of chronic forms in the structure of mortality from circulatory diseases, the absence of significant differences in the structure of strokes, as well as the features of the Tomsk region in the form of high levels of hospitalization profile and hospital case fatality rate, were revealed. The dependence of hospital mortality on logistics is shown, on the basis of which assumptions are made about the possible causes of high fatality rates in the region: excessive centralization of the system of vascular centers and the absence of really working mechanisms for timely reevacuation from them. CONCLUSION To bring chronic circulatory diseases structure in line with international standards, it is necessary to regulate the rules for formulating and coding diagnoses. In order to reduce hospital fatality rates in the Tomsk region, it is necessary to carry out organizational measures: opening a primary vascular department in the area of responsibility of the regional stroke center, as well as strengthening rehabilitation and palliative services for the timely reevacuation of patients from vascular centers.

The aim of the study was directed at studying the sex-specific features of the correlation between genome-wide association studies (GWAS)-noticeable polymorphisms and hypertension (HTN). In two groups of European subjects of Russia (n = 1405 in total), such as men (n = 821 in total: n = 564 HTN, n = 257 control) and women (n = 584 in total: n = 375 HTN, n = 209 control), the distribution of ten specially selected polymorphisms (they have confirmed associations of GWAS level with blood pressure (BP) parameters and/or HTN in Europeans) has been considered. The list of studied loci was as follows: (PLCE1) rs932764 A > G, (AC026703.1) rs1173771 G > A, (CERS5) rs7302981 G > A, (HFE) rs1799945 C > G, (OBFC1) rs4387287 C > A, (BAG6) rs805303 G > A, (RGL3) rs167479 T > G, (ARHGAP42) rs633185 C > G, (TBX2) rs8068318 T > C, and (ATP2B1) rs2681472 A > G. The contribution of individual loci and their inter-locus interactions to the HTN susceptibility with bioinformatic interpretation of associative links was evaluated separately in men’s and women’s cohorts. The men–women differences in involvement in the disease of the BP/HTN-associated GWAS SNPs were detected. Among women, the HTN risk has been associated with HFE rs1799945 C > G (genotype GG was risky; ORGG = 11.15 ppermGG = 0.014) and inter-locus interactions of all 10 examined SNPs as part of 26 intergenic interactions models. In men, the polymorphism BAG6 rs805303 G > A (genotype AA was protective; ORAA = 0.30 ppermAA = 0.0008) and inter-SNPs interactions of eight loci in only seven models have been founded as HTN-correlated. HTN-linked loci and strongly linked SNPs were characterized by pronounced polyvector functionality in both men and women, but at the same time, signaling pathways of HTN-linked genes/SNPs in women and men were similar and were represented mainly by immune mechanisms. As a result, the present study has demonstrated a more pronounced contribution of BP/HTN-associated GWAS SNPs to the HTN susceptibility (due to weightier intergenic interactions) in European women than in men.

Glaucoma remains a leading cause of global irreversible blindness. In the review article by Gao et al., the focus was on intraocular pressure (IOP), which is the only known modifiable risk factor for glaucoma. Genome-wide association studies (GWASs), primarily conducted in European and Asian ancestries, have revealed over 190 genetic loci associated with IOP. Most of these loci were identified through common variants. These findings have led to the development of polygenic scores (PGS) for predicting IOP and glaucoma risk. Recent large-scale exome-wide association studies (ExWAS) have successfully identified rare variants in 40 novel genes, some being noteworthy drug targets for clinical treatment. However, since the majority of GWASs have been conducted in

The development of new drugs is a time consuming and costly process, so the use of approved drugs for new indications (repurposing) is a promising area of development for the pharmaceutical industry. There are two main approaches for drug development: experimental and computational. Currently, due to the availability of large data sets, computational methods, including those based on the use of artificial intelligence, are being actively developed. The widespread use of genetic data in drug development and repurposing has led to the development of such a field of science as pharmacogenetics. The availability of genome-wide association analyses and transcriptome data allow the Mendelian randomization method to be applied to determine the potential for drug repurposing. This article briefly describes the Mendelian randomization method and provides examples of its application to assess the effect of drugs on various diseases.

Purpose:The purpose of this study was to investigate if education contributes to the risk of myopia because educational activities typically occur indoors or because of other factors, such as prolonged near viewing. Methods:This was a two-sample Mendelian randomization study. Participants were from the UK Biobank, Avon Longitudinal Study of Parents and Children, and Generation R. Genetic variants associated with years spent in education or time spent outdoors were used as instrumental variables. The main outcome measures were: (1) spherical equivalent refractive error attained by adulthood, and (2) risk of an early age-of-onset of spectacle wear (EAOSW), defined as an age-of-onset of 15 years or below. Results:Time spent outdoors was found to have a small genetic component (heritability 9.8%) that tracked from childhood to adulthood. A polygenic score for time outdoors was associated with children's time outdoors; a polygenic score for years spent in education was inversely associated with children's time outdoors. Accounting for the relationship between time spent outdoors and myopia in a multivariable Mendelian randomization analysis reduced the size of the causal effect of more years in education on myopia to -0.17 diopters (D) per additional year of formal education (95% confidence interval [CI] = -0.32 to -0.01) compared with the estimate from a univariable Mendelian randomization analysis of -0.27 D per year (95% CI = -0.41 to -0.13). Comparable results were obtained for the outcome EAOSW. Conclusions:Accounting for the effects of time outdoors reduced the estimated causal effect of education on myopia by 40%. These results suggest about half of the relationship between education and myopia may be mediated by children not being outdoors during schooling.

Migrainous stroke is a rare combination of frequently occurring diseases; only a few cases have been described in the domestic literature. The complexity of differential diagnosis is due to the fact that at the stage of initial manifestations, these two conditions can mimic each other. Treatment strategy and further prevention for each of these diseases is different, so timely and convincing early diagnosis is crucial. The presented clinical case describes a case of ischemic stroke in a young woman who had been suffering from migraine for a long time, which did not fully meet the criteria for migrainous infarction. The patient was treated at the regional vascular center of the Tomsk Regional Clinical Hospital, there was a positive trend in the neurological status. The catamnesis of the disease was tracked. It was suggested that endothelial dysfunction is the main pathogenetic factor in the formation of an ischemic focus against the background of a protracted migraine attack.