10 Years of GWAS in intraocular pressure

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, the leading cause of irreversible blindness worldwide. In this review, we summarize the findings of genome-wide association studies (GWASs) of IOP published in the past 10 years and prior to December 2022. Over 190 genetic loci and candidate genes associated with IOP have been uncovered through GWASs, although most of these studies were conducted in subjects of European and Asian ancestries. We also discuss how these common variants have been used to derive polygenic risk scores for predicting IOP and glaucoma, and to infer causal relationship with other traits and conditions through Mendelian randomization. Additionally, we summarize the findings from a recent large-scale exome-wide association study (ExWAS) that identified rare variants associated with IOP in 40 novel genes, six of which are drug targets for clinical treatment or are being evaluated in clinical trials. Finally, we discuss the need for future genetic studies of IOP to include individuals from understudied populations, including Latinos and Africans, in order to fully characterize the genetic architecture of IOP

The effect of the ion beam energy on the properties of indium tin oxide thin films prepared by ion beam assisted deposition

Indium tin oxide (ITO) thin films have been deposited onto polycarbonate substrates by ion beam assisted deposition technique at room temperature. The structural, optical and electrical properties of the films have been characterized by X-ray diffraction, atomic force microscopy, optical transmittance, ellipsometric and Hall effect measurements. The effect of the ion beam energy on the properties of the films has been studied. The optical parameters have been obtained by fitting the ellipsometric spectra. It has been found that high quality ITO film (low electrical resistivity and high optical transmittance) can be obtained at low ion beam energy. In addition, the ITO film prepared at low ion beam energy gives a high reflectance in IR region which is useful for some electromagnetic wave shielding applications.Fundação Calouste Gulbenkia

Exploiting genetics and genomics to improve the understanding of eye diseases [Editorial]

Editorial on the Research Topic Exploiting genetics and genomics to improve the understanding of eye disease

Longitudinal trends in the association of metabolic syndrome with 550 k single-nucleotide polymorphisms in the Framingham Heart Study

We investigated the association of metabolic syndrome (MetS) with a 500 k and a 50 k single-nucleotide polymorphism (SNP) gene chip in the Framingham Heart Study. We cross-sectionally evaluated the MetS longitudinal trends. Data analyzed were from the Offspring Cohort (four exams: first (n = 2,441), third (n = 2,185), fifth (n = 2,308), and seventh (n = 2,328)) and the Generation 3 Cohort (one exam: the first exam (n = 3,997)). The prevalence of MetS was determined using the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, modified with a newly developed correction for medication use. The association test between an SNP and MetS was performed with a generalized estimating equations method under the additive genetic model. Multiple-testing corrections were also performed. The prevalence of MetS in the offspring cohort increased from one visit to the next, and reached the highest point by the seventh exam comparable with the prevalence reported for the general US population. The pattern of the MetS prevalence over time also reflected itself in the association tests, in which the highest significances were seen in the fifth and seventh exams. The association tests showed that SNPs within genes PRDM16, CETP, PTHB1, PAPPA, and FBN3, and also some SNPs not in genes were significant or close to significance at the genome-wide thresholds. These findings are important in terms of eventually identifying with the causal loci for MetS

Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis

The mechanisms that underlie the extensive phenotypic diversity in genetic disorders are poorly understood. Here, we develop a large-scale assay to characterize the functional valence (gain or loss-of-function) of missense variants identified in UBE3A, the gene whose loss-of-function causes the neurodevelopmental disorder Angelman syndrome. We identify numerous gain-of-function variants including a hyperactivating Q588E mutation that strikingly increases UBE3A activity above wild-type UBE3A levels. Mice carrying the Q588E mutation exhibit aberrant early-life motor and communication deficits, and individuals possessing hyperactivating UBE3A variants exhibit affected phenotypes that are distinguishable from Angelman syndrome. Additional structure-function analysis reveals that Q588 forms a regulatory site in UBE3A that is conserved among HECT domain ubiquitin ligases and perturbed in various neurodevelopmental disorders. Together, our study indicates that excessive UBE3A activity increases the risk for neurodevelopmental pathology and suggests that functional variant analysis can help delineate mechanistic subtypes in monogenic disorders

Shyness and Learning Adjustment in Senior High School Students: Mediating Roles of Goal Orientation and Academic Help Seeking

Learning maladjustment is a common phenomenon in the context of examination-oriented education system in china, especially among high school students who experience intense pressure when preparing for the national college entrance examination. Previous literature suggests that shyness may negatively affect ones’ cognition, emotion, and behavioral performance and lead to academic and social maladjustment. Therefore, learning adjustment among shy high school students is a critical and practical point of inquiry. With a sample of 677 Chinese senior high school students, this study aims to assess the association between shyness and learning adjustment and related mechanisms of goal orientation (i.e., mastery-approach goals, mastery-avoid goals, performance-approach goals, and performance-avoid goals) and academic help seeking (i.e., instrumental help seeking from teacher, instrumental help seeking from classmate, executive help seeking, and avoidance of help seeking). Self-report measures were adopted to collect information on: demographic characteristics, the level of shyness, goal orientation, academic help seeking, and learning adjustment. Results indicated that shyness was negatively correlated with learning adjustment, and this association was mediated by the dimensions of goal orientation and dimensions of academic help seeking. Specifically, shyness not only predicted learning adjustment through mastery-approach goals, and instrumental help seeking (teachers) but also predicted learning adjustment through the multiple mediating effects of the dimensions of goal orientation and the dimensions of academic help seeking (i.e., mastery-approach goals and instrumental help seeking from teachers, mastery-approach goals and executive help seeking, mastery-avoid goals and instrumental help seeking from classmates, mastery-avoid goals and executive help seeking, and performance-avoid goals and executive help seeking). Identifying these mediators further enables us to work out effective measures to promote shy high school students’ learning adjustment