Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking.

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).

Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk.

In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBG) 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 SHBG (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-SNP) were taken into account during the "deep study" of the functionality of seven important UF loci and 115 strongly linked [r ≥ 0.

GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma.

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.

Time Spent Outdoors Partly Accounts for the Effect of Education on Myopia.

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.

Association of , polymorphisms with POAG and NTG.

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.

Blood pressure, calcium channel blockers, and the risk of prostate cancer: a Mendelian randomization study.

Background: Observational studies have found some evidence of an association between elevated blood pressure and prostate cancer risk; however, the results are inconclusive. We tested whether systolic blood pressure (SBP) influences prostate cancer risk and evaluated the effect of calcium channel blockers (CCB) on the disease using Mendelian randomization (MR) approach.

Methods: We used 278 genetic variants associated with SBP and 16 genetic variants in CCB genes as instrumental variables.

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia.

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 ( = 1405 in total), such as men ( = 821 in total: = 564 HTN, = 257 control) and women ( = 584 in total: = 375 HTN, = 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: () rs932764 A > G, () rs1173771 G > A, () rs7302981 G > A, () rs1799945 C > G, () rs4387287 C > A, () rs805303 G > A, () rs167479 T > G, () rs633185 C > G, () rs8068318 T > C, and () rs2681472 A > G.

High Blood Pressure and Intraocular Pressure: A Mendelian Randomization Study.

Purpose: To test for causality with regard to the association between blood pressure (BP) and intraocular pressure (IOP) and glaucoma.

Methods: Single nucleotide polymorphisms (SNPs) associated with BP were identified in a genome-wide association study (GWAS) meta-analysis of 526,001 participants of European ancestry. These SNPs were used to assess the BP versus IOP relationship in a distinct sample (n = 70,832) whose corneal-compensated IOP (IOPcc) was measured.

Commonly occurring genetic polymorphisms with a major impact on the risk of nonsyndromic strabismus: replication in a sample from Finland.

Purpose: To replicate associations between polymorphisms in the WRB and TSPAN10 genes and strabismus in an independent Finnish cohort and to calculate their population attributable risk.

Methods: Polymorphisms in the WRB (rs2244352) and TSPAN10 (rs6420484) genes were investigated in individuals from the FinnGen study group who had one of three categories of strabismus, with clinical diagnoses of (1) "strabismus-all subtypes" (3,515 cases and 173,384 controls), (2) "convergent concomitant strabismus" (ICD-10 code H50.0; 737 cases and 170,976 controls), and (3) "divergent concomitant strabismus" (ICD-10 code H50.

Hyperopia Is Not Causally Associated With a Major Deficit in Educational Attainment.

Purpose: Hyperopia (farsightedness) has been associated with a deficit in children's educational attainment in some studies. We aimed to investigate the causality of the relationship between refractive error and educational attainment.

Methods: Mendelian randomization (MR) analysis in 74,463 UK Biobank participants was used to estimate the causal effect of refractive error on years spent in full-time education, which was taken as a measure of educational attainment.

Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to Myopia.

Purpose: Emmetropization requires coordinated scaling of the major ocular components, corneal curvature and axial length. This coordination is achieved in part through a shared set of genetic variants that regulate eye size. Poorly coordinated scaling of corneal curvature and axial length results in refractive error.

Effect of Education on Myopia: Evidence from the United Kingdom ROSLA 1972 Reform.

Purpose: Cross-sectional and longitudinal studies have consistently reported an association between education and myopia. However, conventional observational studies are at risk of bias due to confounding by factors such as socioeconomic position and parental educational attainment. The current study aimed to estimate the causal effect of education on refractive error using regression discontinuity analysis.

Association Between Polygenic Risk Score and Risk of Myopia.

Importance: Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention.

Objectives: To examine whether genetic information alone can identify children at risk of myopia development and whether including a child's genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia.

Association between birth weight and refractive error in adulthood: a Mendelian randomisation study.

Background: Pathological myopia is one of the leading causes of blindness globally. Lower birth weight (BW) within the normal range has been reported to increase the risk of myopia, although findings conflict. We sought to estimate the causal effect of BW on refractive error using Mendelian randomisation (MR), under the assumption of a linear relationship.

A commonly occurring genetic variant within the NPLOC4-TSPAN10-PDE6G gene cluster is associated with the risk of strabismus.

Strabismus refers to an abnormal alignment of the eyes leading to the loss of central binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. As such, it is inherited as a complex genetic trait, affecting 2-4% of the population.

Mendelian randomisation and the goal of inferring causation from observational studies in the vision sciences.

Purpose: Randomised controlled trials (RCTs) allow reliable causal inferences to be drawn regarding the effectiveness of specific interventions. However, they are expensive to carry out, and not all exposure-outcome relationships can be tested in an RCT framework: for example, it would be unethical to deliberately expose participants to a putative risk factor, or the time-scale involved may be prohibitive. Mendelian randomisation (MR) has been proposed as an alternative approach for drawing causal inferences, with the major advantage that the method can often be applied to existing, cross-sectional study datasets.

Education and myopia: assessing the direction of causality by mendelian randomisation.

Objectives: To determine whether more years spent in education is a causal risk factor for myopia, or whether myopia is a causal risk factor for more years in education.

Design: Bidirectional, two sample mendelian randomisation study.

Setting: Publically available genetic data from two consortiums applied to a large, independent population cohort.