Focusing in on the complex genetics of myopia.
Ontology highlight
ABSTRACT:
SUBMITTER: Wojciechowski R
PROVIDER: S-EPMC3617090 | biostudies-literature | 2013 Apr
REPOSITORIES: biostudies-literature
Publications
Focusing in on the complex genetics of myopia.
Wojciechowski Robert R Hysi Pirro G PG
PLoS genetics 20130404 4
Similar Datasets
Project description:The refractive errors, myopia and hyperopia, are optical defects of the visual system that can cause blurred vision. Uncorrected refractive errors are the most common causes of visual impairment worldwide. It is estimated that 2.5 billion people will be affected by myopia alone within the next decade. Experimental, epidemiological and clinical research has shown that refractive development is influenced by both environmental and genetic factors. Animal models have showed that eye growth and refractive maturation during infancy are tightly regulated by visually guided mechanisms. Observational data in human populations provide compelling evidence that environmental influences and individual behavioral factors play crucial roles in myopia susceptibility. Nevertheless, the majority of the variance of refractive error within populations is thought to be because of hereditary factors. Genetic linkage studies have mapped two dozen loci, while association studies have implicated more than 25 different genes in refractive variation. Many of these genes are involved in common biological pathways known to mediate extracellular matrix (ECM) composition and regulate connective tissue remodeling. Other associated genomic regions suggest novel mechanisms in the etiology of human myopia, such as mitochondrial-mediated cell death or photoreceptor-mediated visual signal transmission. Taken together, observational and experimental studies have revealed the complex nature of human refractive variation, which likely involves variants in several genes and functional pathways. Multiway interactions between genes and/or environmental factors may also be important in determining individual risks of myopia, and may help explain the complex pattern of refractive error in human populations.
| S-EPMC3058260 | biostudies-literature
Project description:Myopia is the most common eye condition leading to visual impairment and is greatly influenced by genetics. Over the last two decades, more than 400 associated gene loci have been mapped for myopia and refractive errors via family linkage analyses, candidate gene studies, genome-wide association studies (GWAS), and next-generation sequencing (NGS). Lifestyle factors, such as excessive near work and short outdoor time, are the primary external factors affecting myopia onset and progression. Notably, besides becoming a global health issue, myopia is more prevalent and severe among East Asians than among Caucasians, especially individuals of Chinese, Japanese, and Korean ancestry. Myopia, especially high myopia, can be serious in consequences. The etiology of high myopia is complex. Prediction for progression of myopia to high myopia can help with prevention and early interventions. Prediction models are thus warranted for risk stratification. There have been vigorous investigations on molecular genetics and lifestyle factors to establish polygenic risk estimations for myopia. However, genes causing myopia have to be identified in order to shed light on pathogenesis and pathway mechanisms. This report aims to examine current evidence regarding (1) the genetic architecture of myopia; (2) currently associated myopia loci identified from the OMIM database, genetic association studies, and NGS studies; (3) gene-environment interactions; and (4) the prediction of myopia via polygenic risk scores (PRSs). The report also discusses various perspectives on myopia genetics and heredity.
| S-EPMC8947159 | biostudies-literature
Project description:The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth.
| S-EPMC6892384 | biostudies-literature
Project description:Myopia is a significant public health problem and its prevalence is increasing over time and genetic factors in disease development are important. The prevalence and incidence of myopia within sampled population often varies with age, country, sex, race, ethnicity, occupation, environment, and other factors. Myopia growth is under a combination of genes and their products in time and space to complete the coordination role of the guidance. Myopia-related genes include about 70 genetic loci to which primary myopias have been mapped, although the number is constantly increasing and depends to some extent on definition. Of these, several are associated with additional abnormalities, mostly as part of developmental syndromes. These tend to result from mutations in genes encoding transcriptional activators, and most of these have been identified by sequencing candidate genes in patients with developmental anomalies. Currently, COL1A1 (collagen alpha-1 chain of type I), COL2A1 (collagen alpha-1 chain of type II), ACTC1 (actin, alpha, cardiac muscle 1), PAX6 (paired box gene 6) and NIPBL (nipped-B homolog), and so on have been mapped. Myopia is most commonly treated with spectacles or glasses. The most common surgical procedure performed to correct myopia is laser in situ keratomileusis (LASIK). This review of the recent advances on epidemiology, genetic locations and treatments of myopia are summarized.
| S-EPMC3340784 | biostudies-literature
Project description:Myopia, or nearsightedness, is the most common human eye disorder in the world, and is a significant global public health concern. Along with cataract, macular degeneration, infectious disease, and vitamin A deficiency, myopia is one of the most important causes of visual impairment worldwide. Severe or high-grade myopia is a leading cause of blindness because of its associated ocular morbidities of retinal detachment, macular choroidal degeneration, premature cataract, and glaucoma. Ample evidence documents the heritability of the non-syndromic forms of this condition, especially for high-grade myopia, commonly referred to as myopic spherical refractive power of 5 to 6 diopters or higher. Multiple high-grade myopia genetic loci have been identified, and confirmatory studies identifying high-grade and moderate myopia loci have also occurred. In general, myopia susceptibility genes are unknown with few association studies performed, and without confirmation in other research laboratories or testing of separate patient cohorts.
| S-EPMC3718050 | biostudies-literature
Project description:Myopia is the most common cause of visual impairment worldwide. Genetic and environmental factors contribute to the development of myopia. Studies on the molecular genetics of myopia are well established and have implicated the important role of genetic factors. With linkage analysis, association studies, sequencing analysis, and experimental myopia studies, many of the loci and genes associated with myopia have been identified. Thus far, there has been no systemic review of the loci and genes related to non-syndromic and syndromic myopia based on the different approaches. Such a systemic review of the molecular genetics of myopia will provide clues to identify additional plausible genes for myopia and help us to understand the molecular mechanisms underlying myopia. This paper reviews recent genetic studies on myopia, summarizes all possible reported genes and loci related to myopia, and suggests implications for future studies on the molecular genetics of myopia.
| S-EPMC5757860 | biostudies-literature
Project description:Myopia is a complex inherited ocular trait resulting from an interplay of genes and environmental factors, most of which are currently unknown. In two independent population-based cohorts consisting of 5,256 and 3,938 individuals from European descent, we tested for biological interaction between genetic predisposition and level of education on the risk of myopia. A genetic risk score was calculated based on 26 myopia-associated single nucleotide polymorphisms recently discovered by the Consortium for Refractive Error and Myopia. Educational level was obtained by questionnaire and categorized into primary, intermediate, and higher education. Refractive error was measured during a standardized ophthalmological examination. Biological interaction was assessed by calculation of the synergy index. Individuals at high genetic risk in combination with university-level education had a remarkably high risk of myopia (OR 51.3; 95 % CI 18.5-142.6), while those at high genetic risk with only primary schooling were at a much lower increased risk of myopia (OR 7.2, 95 % CI 3.1-17.0). The combined effect of genetic predisposition and education on the risk of myopia was far higher than the sum of these two effects (synergy index 4.2, 95 % CI 1.9-9.5). This epidemiological study provides evidence of a gene-environment interaction in which an individual's genetic risk of myopia is significantly affected by his or her educational level.
| S-EPMC3898347 | biostudies-literature
Project description:To aim of the study was describe the growth of publications on genetic myopia and understand the current research landscape through the analysis of citation networks, as well as determining the different research areas and the most cited publications. The Web of Science database was used to perform the publication search, looking for the terms "genetic*" AND "myopia" within the period between 2009 and October 2020. The CitNetExplorer and CiteSpace software were then used to conduct the publication analysis. To obtain the graphics, the VOSviewer software was used. A total of 721 publications were found with 2999 citations generated within the network. The year 2019 was singled out as a "key year", taking into account the number of publications that emerged in that year and given that in 2019, 200 loci associated with refractive errors and myopia were found, which is considered to be great progress. The most widely cited publication was "Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia", an article by Verhoeven et al., which was published in 2013. By using the clustering function, we were able to establish three groups that encompassed the different research areas within this field: heritability rate of myopia and its possible association with environmental factors, retinal syndromes associated with myopia and the genetic factors that control and influence axial growth of the eye. The citation network offers a comprehensive and objective analysis of the main papers that address genetic myopia.
| S-EPMC8003911 | biostudies-literature
Project description:Many epidemiological and experimental studies have established that myopia is caused by a complex interaction between common genetic and environmental factors. The objective of this study was to describe and compare the allelic and genotypic frequencies of the rs524952 (GJD2), rs8000973 (ZIC2), rs1881492 (CHRNG), rs1656404 (PRSS56), rs235770 (BMP2), and rs7744813 (KCNQ5) SNPs (single-nucleotide polymorphism) between responder and nonresponder patients who had undergone a two-year treatment with lenses for myopia control. Twenty-eight participants from the MiSight Assessment Study Spain (MASS), who had received treatment for myopia control for two years with MiSight contact lenses, were examined. The criteria for better/worse treatment response was the change in the axial length (< / ≥ 0.22 mm two years after the treatment). The clinical procedure consisted of the extraction of a saliva sample, and the participants also underwent an optometric examination. Genetic data were analyzed using SNPStats software (Catalan Institute of Oncology, Barcelona, Spain), and statistical analysis was performed using SPSS v.25 (SPSS Inc., Chicago, IL, USA). Demographic variables were analyzed using the Student's t-test. The T allele, the one with the lowest frequency, of the "rs235770" SNP was associated with a better treatment response [AL/CR (axial length/corneal radius): OR = 3.37; CI = 1.079-10.886; SE (spherical equivalent): OR = 1.26; CI: = 0.519-57.169; p = 0.019). By performing haplotype analysis, significant differences were found between the rs235770…rs1881492 and rs235770-rs1656404 polymorphisms. The latter presented a strong linkage disequilibrium with each other (r2 ≥ 0.54). The result of lens therapies for myopia control could vary depending on genetic variants. Studies with a larger sample are needed to confirm the results presented in this pilot study.
| S-EPMC7922351 | biostudies-literature
Project description:Myopia, or nearsightedness, is the most common human eye disorder in the world and is a significant global public health concern. Along with cataract, macular degeneration, infectious disease, and vitamin A deficiency, myopia is one of the most important causes of visual impairment worldwide. Severe or high-grade myopia is a leading cause of blindness because of its associated ocular comorbidities of retinal detachment, macular choroidal degeneration, premature cataract, and glaucoma. Ample epidemiologic and molecular genetic studies support heritability of the nonsyndromic forms of this condition.Multiple myopia genetic loci have been identified, establishing this entity as a common complex disorder and underscoring the suitability for gene inquiry studies. Animal model research, primarily using form-deprivation techniques, implicates multiple altered regulation of biological substances in the ocular wall layers, which provides important information for prioritizing human candidate gene studies. Recent epidemiologic work supports a greater role for outdoor activity in relieving myopia progression rather than the previous touted young-age near-work activity model.The identification of myopia susceptibility genes will not only provide insight into the molecular basis of this significant eye disorder, but will also identify pathways involved in eye growth and development. This effort may lead to effective therapies to treat or potentially prevent this common eye condition.
| S-EPMC3736551 | biostudies-literature