Summary
This research article examined how genetic variants interact with education level to influence susceptibility to myopia (nearsightedness). The study involved two large samples of unrelated Europeans from the UK Biobank study. In the first sample, the authors performed a genome-wide association study (GWAS) for refractive error, followed by tests for genetic variants associated with differences in refractive error variance between genotypes. This identified 25 genetic variants enriched for potential gene-environment (GxE) interactions. In the second sample, tests showed 6 of these variants had significant genotype-by-education level interactions affecting risk of myopia. For all 6 variants, more years of education strengthened the effect of the myopia risk allele. Three variants (in GJD2, RBFOX1 and LAMA2) replicated previous findings, while three were novel discoveries implicating the genes KCNQ5, LRRC4C and TOX.
Overall, the study identified genetic factors where exposure to additional years of education increased their impact on myopia risk. The implicated genes have diverse functions in the visual system, including neuronal development. This highlights biological pathways by which intensive education may trigger excessive eye growth and myopia development.
Key Facts
- The study involved two large samples totaling over 300,000 Europeans from the UK Biobank cohort.
- A two-step screening process identified 25 genetic variants enriched for gene-environment interactions influencing refractive error.
- 6 variants showed significant genotype-by-education level interactions affecting myopia risk, with 3 being novel discoveries.
- For all 6 variants, more years of education strengthened the effect of the myopia risk allele.
Source: PLOS Genetics
New Study Finds “Back-to-School” Boosts Genetic Risk of Myopia
This research article examined whether genetic variants interacted with education level to influence an individual’s susceptibility to developing myopia (nearsightedness). Myopia is a common refractive error of the eye caused by a mismatch between the axial length and optical power of the eye. Uncorrected myopia impairs distance vision and increases risk of multiple eye disorders. The prevalence of myopia has rapidly increased over recent decades, linked to changes in lifestyle factors including more intensive education systems. Both genetic and environmental factors are known to contribute to myopia risk. However, there has been limited study of how genetic variants may interact with environmental exposures like education to affect susceptibility.
To investigate potential gene-environment (GxE) interactions influencing myopia, the authors performed a large genome-wide association study using two independent samples of Europeans from the UK Biobank cohort. The first sample of over 88,000 participants had refractive error measured by autorefraction. The second sample of over 252,000 participants self-reported their age when they first needed glasses, which served as a surrogate measure of refractive error. The authors first conducted a genome-wide screen in the first sample to identify genetic variants associated with differences in refractive error variance between genotypes. This screening method enriches for variants exhibiting GxE interactions. Twenty-five genetic variants with evidence of variance heterogeneity were identified. Nineteen of these variants (76%) also showed variance heterogeneity for age of glasses wear in the second sample, confirming most were true positives.
The 25 variants were then tested for genotype-by-education level interactions in the second sample. Years of education was used as a proxy for intensity of near work and education during childhood. Six variants showed significant interactions after accounting for multiple testing. For all six, having more years of education strengthened the effect of the myopia risk allele. Three variants were located in the GJD2, RBFOX1 and LAMA2 genes; previous studies also found these variants exhibited gene-education interactions for myopia. The other three variants implicated novel myopia susceptibility genes: KCNQ5, LRRC4C and TOX. Analyses confirmed the interaction effects were not explained by correlations between genotype and education level. Overall, the study identified several genetic factors where exposure to additional years of intensive education triggered a stronger impact on myopia risk. The implicated genes have diverse functions relevant to myopia, including roles in neuronal development, axon guidance, and formation of neural circuits in the visual system.
A key strength of the study was the very large sample size, which provided high statistical power to detect GxE interactions. The authors also used multiple methods to validate their findings. A limitation was that participants were aged 40-70 years, and had undergone education several decades previously when fewer years were spent in education. Testing younger cohorts from contemporary education systems may reveal additional gene-education interactions. In conclusion, this study identified novel genetic variants interacting with education level to affect myopia risk. A better understanding of these gene-environment interactions and the underlying biological mechanisms will be important for developing strategies to reduce the increasing prevalence of myopia worldwide.
About this genes and education level affect on myopia research news
Author: Rosie Clark ,Alfred Pozarickij ,Pirro G. Hysi,Kyoko Ohno-Matsui,Cathy Williams,Jeremy A. Guggenheim ,UK Biobank Eye and Vision Consortium
Source: PLOS Genetics
Contact: PLOS Genetics
Image: The image is credited to Myopio News
Abstract
Myopia most often develops during school age, with the highest incidence in countries with intensive education systems. Interactions between genetic variants and educational exposure are hypothesized to confer susceptibility to myopia, but few such interactions have been identified. Here, we aimed to identify genetic variants that interact with education level to confer susceptibility to myopia. Two groups of unrelated participants of European ancestry from UK Biobank were studied. A ‘Stage-I’ sample of 88,334 participants whose refractive error (avMSE) was measured by autorefraction and a ‘Stage-II’ sample of 252,838 participants who self-reported their age-of-onset of spectacle wear (AOSW) but who did not undergo autorefraction. Genetic variants were prioritized via a 2-step screening process in the Stage-I sample: Step 1 was a genome-wide association study for avMSE; Step 2 was a variance heterogeneity analysis for avMSE. Genotype-by-education interaction tests were performed in the Stage-II sample, with University education coded as a binary exposure. On average, participants were 58 years-old and left full-time education when they were 18 years-old; 35% reported University level education. The 2-step screening strategy in the Stage-I sample prioritized 25 genetic variants (GWAS P < 1e-04; variance heterogeneity P < 5e-05). In the Stage-II sample, 19 of the 25 (76%) genetic variants demonstrated evidence of variance heterogeneity, suggesting the majority were true positives. Five genetic variants located near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C had evidence of a genotype-by-education interaction in the Stage-II sample (P < 0.002) and consistent evidence of a genotype-by-education interaction in the Stage-I sample. For all 5 variants, University-level education was associated with an increased effect of the risk allele. In this cohort, additional years of education were associated with an enhanced effect of genetic variants that have roles including axon guidance and the development of neuronal synapses and neural circuits.