Genetic and environmental effects on myopia development and progression.
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ABSTRACT:
SUBMITTER: Goldschmidt E
PROVIDER: S-EPMC3930266 | biostudies-other | 2014 Feb
REPOSITORIES: biostudies-other
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Project description:ObjectiveThe purpose of this study was to evaluate the effect of genetic-environmental interaction on myopia in Chinese children aged 6 to 9 years.MethodsStudents had the physical examination and were required to provide basic demographic information. Their families were asked to fill in a questionnaire concerning factors related to myopia. Multiple regression analysis was performed, and adjusted risk ratio values were calculated to assess the role between gene and environment. Value of the environmental and genetic index (EGI) was calculated to demonstrate the effect of genetic-environmental interaction on myopia.ResultsThe prevalence of myopia maintained at a high level. EGI was calculated as 0.125 suggesting that genetic factors may play the 12.5% role in the formation of myopia and environmental factors may play a role of 87.5% in the formation of myopia.ConclusionsFor young pupils aged 6 to 9 years, myopia prevalence maintained at a high level, and duration of homework time and staring at electronic screen were the strongest factors associated with myopia. The calculated value of EGI was low, which suggests that environmental factors may play the leading role in the formation of myopia. A long-term follow-up research to improve the accuracy value of EGI is our next job.
| S-EPMC7670298 | biostudies-literature
Project description:Researchers have identified sources of individual differences in writing across beginning and developing writers. The aim of the present study was to further clarify the sources of this variability by investigating the extent to which there are differences in genetic and environmental factors underlying the associations between lexical diversity, syntactic knowledge, and semantic cohesion knowledge in relation to writing. Differences were examined across two developmental phases of writing: beginning (i.e., elementary school) and developing (i.e., middle school). Participants included 262 twin pairs (Mage = 10.88 years) in elementary school and 247 twin pairs (Mage = 13.21 years) in middle school. Twins were drawn from the Florida Twin Project on Reading, Behavior, and Environment. Biometric models were conducted separately for subgroups defined by phase of writing development. Results indicated significant etiological differences in writing components across the two phases, such that effects associated with genes and non-shared environment were greater while effects associated with shared environment were lower in developing writers as compared to beginning writers. Furthermore, results showed that child-specific environment was the largest contributor to individual differences in writing components and their covariation for both beginning and developing writers. These results imply that even direct instruction about writing in schools may be having different effects on children based on their unique experiences.
| S-EPMC5739064 | biostudies-literature
Project description:ObjectiveTo investigate annual myopia progression in individuals from South Indian states across different age groups, and its association with age of onset and severity of myopia.MethodsThis retrospective study included the data of 6984 myopes (range: 1-30 years), who visited at least twice to LV Prasad Eye Institute and on whom a standard retinoscopy technique was performed to determine refractive error. Based on spherical equivalent (SE) refractive error, individuals were classified into mild, moderate, high and severe myopic groups. Myopia progression was calculated as difference between SE at 1-year follow-up visit and at baseline. To determine the age-specific myopia progression, individuals were further categorized as myopes who are at least 15 years or younger and those who are above 15.ResultsThe mean annual progression of myopia was influenced by both the age group (p < 0.001) and severity type of myopia (p < 0.001). The overall mean myopia progression ranged from -0.07 ± 0.02 D (standard error) to -0.51 ± 0.02 D across different age groups with maximum change in refractive error noted in children aged 6-10 years and the least in adults aged 26-30 years. Myopia progression was greater in severe myopes, followed by high, moderate, mild myopes and in individuals aged ≤ 15 years compared to those aged >15 years (-0.45 ± 0.01 vs. 0.14 ± 0.01, p < 0.001). Severe myopes alone had similar annual myopia progression rate irrespective of age (i.e ≤15 and >15 years, p = 0.71). Early onset of myopia was associated with high myopia in adulthood.ConclusionThe magnitude of myopia progression in children from South Indian states is comparable to that of Caucasians and Chinese. The greater progression in 'severe myopes' across different age groups emphasize the need for regular follow-ups, monitoring axial lengths, and anti-myopia strategies to control myopia progression irrespective of the age and degree of myopia.
| S-EPMC7678965 | biostudies-literature
Project description:PurposeTo test the hypothesis that emmetropization buffers against genetic and environmental risk factors for myopia by investigating whether risk factor effect sizes vary depending on children's position in the refractive error distribution.MethodsRefractive error was assessed in participants from two birth cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) (noncycloplegic autorefraction) and Generation R (cycloplegic autorefraction). A genetic risk score for myopia was calculated from genotypes at 146 loci. Time spent reading, time outdoors, and parental myopia were ascertained from parent-completed questionnaires. Risk factors were coded as binary variables (0 = low, 1 = high risk). Associations between refractive error and each risk factor were estimated using either ordinary least squares (OLS) regression or quantile regression.ResultsQuantile regression: effects associated with all risk factors (genetic risk, parental myopia, high time spent reading, low time outdoors) were larger for children in the extremes of the refractive error distribution than for emmetropes and low ametropes in the center of the distribution. For example, the effect associated with having a myopic parent for children in quantile 0.05 vs. 0.50 was as follows: ALSPAC: age 15, -1.19 D (95% CI -1.75 to -0.63) vs. -0.13 D (-0.19 to -0.06), P = 0.001; Generation R: age 9, -1.31 D (-1.80 to -0.82) vs. -0.19 D (-0.26 to -0.11), P < 0.001. Effect sizes for OLS regression were intermediate to those for quantiles 0.05 and 0.50.ConclusionsRisk factors for myopia were associated with much larger effects in children in the extremes of the refractive error distribution, providing indirect evidence that emmetropization buffers against both genetic and environmental risk factors.
| S-EPMC7329625 | biostudies-literature
Project description:Following laboratory and clinical findings implicating circadian biology in the pathogenesis of myopia (nearsightedness), we examined gene expression in two crucial tissues controlling post-natal refractive development, the retina and choroid. Inducing unilateral visual form deprivation myopia in young chicks, a widely studied and validated model, we isolated retinal and choroidal tissues every 4 hours over a single day from myopic and contralateral control eyes during a period time when myopia progresses rapidly.
2024-07-01 | GSE261232 | GEO
Project description:Genetic alterations in the INK4a/ARF (or CDKN2A) locus have been reported in many cancer types, including melanoma; head and neck squamous cell carcinomas; lung, breast, and pancreatic cancers. In melanoma, loss of function CDKN2A alterations have been identified in approximately 50% of primary melanomas, in over 75% of metastatic melanomas, and in the germline of 40% of families with a predisposition to cutaneous melanoma. The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin-dependent kinase inhibitor p16INK4a and the p53 regulator p14ARF. The majority of CDKN2A alterations in melanoma selectively target p16INK4a or affect the coding sequence of both p16INK4a and p14ARF. There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14ARF, while not altering the syntenic p16INK4a coding regions. In this review, we describe the frequency and types of somatic alterations affecting the CDKN2A locus in melanoma and germline CDKN2A alterations in familial melanoma, and their functional consequences in melanoma development. We discuss the clinical implications of CDKN2A inactivating alterations and their influence on treatment response and resistance.
| S-EPMC7602651 | biostudies-literature
Project description:ImportanceGiven the estimates of increasing prevalence of myopia, especially in Asia, it is important to determine the current prevalence of myopia among populations of schoolchildren in Japan.ObjectiveTo investigate the current prevalence rate of myopia and the association between environmental factors and myopia in Japanese schoolchildren.Design, setting, and participantsThis cross-sectional study assessed 1478 participants, including 726 elementary school students and 752 junior high school students, at 2 schools in Tokyo, Japan, who underwent eye examinations from April 1 to May 31, 2017, that included measurement of the refractive errors by autorefractometry with noncycloplegic refraction and ocular biometric factors. After excluding those who had been treated with atropine or orthokeratology (n = 11), had a history of eye disease (n = 2), had no parental consent (n = 41), and were absent (n = 8), 1416 schoolchildren were analyzed.Main outcomes and measuresThe primary outcome was the prevalence of myopia and high myopia. Secondary outcomes were environmental factors that were associated with myopia.ResultsA total of 1416 schoolchildren (mean [SD] age, 10.8 [2.7] years; 792 [55.9%] male) were studied. The prevalence rates of myopia (spherical equivalent ≤-0.5 diopters [D]) were 76.5% (95% CI, 73.4%-79.7%) among the elementary school students and 94.9% (95% CI, 93.3%-96.5%) among the junior high school students. The prevalence rates of high myopia (spherical equivalent ≤-6.0 D) were 4.0% (95% CI, 2.5%-5.4%) among the elementary school students and 11.3% (95% CI, 8.8%-13.7%) among the junior high school students. The prevalence rates of high myopia classified based on axial length of 26.0 mm or longer were 1.2% (95% CI, 0.4%-2.0%) among elementary school students and 15.2% (95% CI, 12.5%-17.8%) among junior high school students. Multiple regression analysis showed that higher-order aberrations and dry eye disease were associated with refractive error in elementary school students (spherical aberration: β = 6.152; 95% CI, 3.161-9.143; P < .001; dry eye disease: β = -0.626; 95% CI, -1.189 to -0.063; P = .03) and with axial length in junior high school students (spherical-like aberration: β = 26.546; 95% CI, 18.708-34.385; P < .001; dry eye disease: β = 0.354; 95% CI, 0.131-0.578; P < .002).Conclusions and relevanceAlthough the use of noncycloplegic autorefraction with a cutoff of -0.50 D could lead to overestimation of results, these findings suggest that the current prevalence rates of myopia among elementary and junior high school students in Asia are high, especially if the results from these 2 schools are generalizable to all schoolchildren in Japan and Asia.
| S-EPMC6696729 | biostudies-literature
Project description:Genome-wide association studies (GWAS) have revealed that the genetic contribution to certain complex diseases is well-described by Fisher's infinitesimal model in which a vast number of polymorphisms each confer a small effect. Under Fisher's model, variants have additive effects both across loci and within loci. However, the latter assumption is at odds with the common observation of dominant or recessive rare alleles responsible for monogenic disorders. Here, we searched for evidence of non-additive (dominant or recessive) effects for GWAS variants known to confer susceptibility to the highly heritable quantitative trait, refractive error. Of 146 GWAS variants examined in a discovery sample of 228,423 individuals whose refractive error phenotype was inferred from their age-of-onset of spectacle wear, only 8 had even nominal evidence (p < 0.05) of non-additive effects. In a replication sample of 73,577 individuals who underwent direct assessment of refractive error, 1 of these 8 variants had robust independent evidence of non-additive effects (rs7829127 within ZMAT4, p = 4.76E-05) while a further 2 had suggestive evidence (rs35337422 in RD3L, p = 7.21E-03 and rs12193446 in LAMA2, p = 2.57E-02). Accounting for non-additive effects had minimal impact on the accuracy of a polygenic risk score for refractive error (R2 = 6.04% vs. 6.01%). Our findings demonstrate that very few GWAS variants for refractive error show evidence of a departure from an additive mode of action and that accounting for non-additive risk variants offers little scope to improve the accuracy of polygenic risk scores for myopia.
| S-EPMC7297706 | biostudies-literature
Project description:BackgroundMyopia is a good model for understanding the interaction between genetics and environmental stimuli. Here we dissect the biological processes affecting myopia progression.MethodsHuman Genetic Analyses: (1) gene set analysis (GSA) of new genome wide association study (GWAS) data for 593 individuals with high myopia (refraction ≤ -6 diopters [D]); (2) over-representation analysis (ORA) of 196 genes with de novo mutations, identified by whole genome sequencing of 45 high-myopia trio families, and (3) ORA of 284 previously reported myopia risk genes. Contributions of the enriched signaling pathways in mediating the genetic and environmental interactions during myopia development were investigated in vivo and in vitro.ResultsAll three genetic analyses showed significant enrichment of four KEGG signaling pathways, including amphetamine addiction, extracellular matrix (ECM) receptor interaction, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton pathways. In individuals with extremely high myopia (refraction ≤ -10 D), the GSA of GWAS data revealed significant enrichment of the HIF-1α signaling pathway. Using human scleral fibroblasts, silencing the key nodal genes within protein-protein interaction networks for the enriched pathways antagonized the hypoxia-induced increase in myofibroblast transdifferentiation. In mice, scleral HIF-1α downregulation led to hyperopia, whereas upregulation resulted in myopia. In human subjects, near work, a risk factor for myopia, significantly decreased choroidal blood perfusion, which might cause scleral hypoxia.InterpretationOur study implicated the HIF-1α signaling pathway in promoting human myopia through mediating interactions between genetic and environmental factors.FundingNational Natural Science Foundation of China grants; Natural Science Foundation of Zhejiang Province.
| S-EPMC7348000 | biostudies-literature
Project description:Late-onset Alzheimer's disease (LOAD) is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.
| S-EPMC5562669 | biostudies-other