Dataset Information

In-utero epigenetic factors are associated with early-onset myopia in young children.

ABSTRACT:

Objectives

To assess whether epigenetic mechanisms affecting gene expression may be involved in the pathogenesis of early-onset myopia, we performed genome-wide DNA methylation analyses of umbilical cord tissues, and assessed any associations between CpG site-specific methylation and the development of the disorder when the children were 3 years old.

Methods

Genome-wide DNA methylation profiling of umbilical cord samples from 519 Singaporean infants involved in a prospective birth cohort 'Growing Up in Singapore Towards healthy Outcomes' (GUSTO) was performed using the Illumina Infinium HumanMethylation450K chip microarray. Multivariable logistic regression models were used to assess any associations between site-specific CpG methylation of umbilical cord tissue at birth and myopia risk in 3 year old children, adjusting for potential confounders. Gene expression of genes located near CpG sites that demonstrated statistically significant associations were measured in relevant ocular tissues using human and mouse fetal and adult eye samples.

Results

We identified statistically significant associations between DNA methylation levels at five CpG sites and early-onset myopia risk after correcting for multiple comparisons using a false discovery rate of 5%. Two statistically significant CpG sites were identified in intergenic regions: 8p23(p = 1.70×10-7) and 12q23.2(p = 2.53×10-7). The remaining 3 statistically significant CpG sites were identified within the following genes: FGB (4q28, p = 3.60×10-7), PQLC1 (18q23, p = 8.9×10-7) and KRT12 (17q21.2, p = 1.2×10-6). Both PQLC1 and KRT12 were found to be significantly expressed in fetal and adult cornea and sclera tissues in both human and mouse.

Conclusions

We identified five CpG methylation sites that demonstrate a statistically significant association with increased risk of developing early-onset myopia. These findings suggest that variability in the neonatal cord epigenome may influence early-onset myopia risk in children. Further studies of the epigenetic influences on myopia risk in larger study populations, and the associations with adulthood myopia risk are warranted.

SUBMITTER: Seow WJ

PROVIDER: S-EPMC6524791 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceMyopia has reached epidemic levels among children in regions of East and Southeast Asia. High myopia is associated with myopic macular degeneration, glaucoma, and retinal detachment.ObjectiveTo determine the incidence of myopia and high myopia based on refraction without cycloplegia among children in primary and junior high schools in China.Design, setting, and participantsThis observational cohort study was completed in Guangzhou, China. It consisted of a cohort from 19 primary schools, who were followed up from 2010 to 2015, and a cohort from 22 junior high schools, who were followed up from 2010 to 2012. All schools were randomly chosen at rates proportional to the number of schools in each of the city's 11 districts. Students with or without myopia in grade 1 (primary school) or grade 7 (junior high school) were eligible for inclusion. Data analysis occurred from February 2017 to October 2017.Main outcomes and measuresMyopia was defined as a spherical equivalent refraction (SER) of -0.50 diopters (D) or less, as measured by subjective refraction without cycloplegia; high myopia was defined as a SER of -6.0 D or less. Annual incidences were defined as the proportion of participants each year found to have myopia or high myopia who did not previously have the condition. Height, weight, axial length (AL), corneal radius of curvature (CRC), and AL/CRC ratio were examined to assess if these measures were associated with future myopia or high myopia.ResultsA total of 4741 students with or without myopia in either grade 1 for the primary school cohort (mean [SD] age 7.2 [0.4] years; 932 of 1975 [47.2%] female) or grade 7 for the junior high school cohort (mean [SD] age 13.2 [0.5] years; 1254 of 2670 [47.0%] female) were included. Baseline mean (SD) SER was 0.31 (0.86) D among 1975 students in grade 1 vs -1.60 (2.00) D among 2670 students in grade 7. Baseline prevalence of myopia was 12.0% in grade 1 students (n = 237 of 1969) and 67.4% in grade 7 students (n = 1795 of 2663). The incidence of myopia was 20% to 30% each year throughout both cohorts. The incidence of high myopia was initially less than 1% in the primary school cohort (grade 1: n = 2 of 1825; 0.1% [95% CI, 0.0%-0.3%]), but incidence exceeded 2% in the junior high school cohort (in grade 9: n = 48 of 2044; 2.3% [95% CI, 1.0%-3.7%]).Conclusions and relevanceThe incidence of myopia among Chinese students based on refraction without cycloplegia is among the highest of any cultural or ethnic group. If confirmed with cycloplegic refraction, interventions to prevent myopia onset in Chinese populations should be initiated in primary schools.

Project description:Background & aimsThe incidence of colorectal cancer (CRC) is increasing in individuals younger than 50 years, who do not usually undergo screening if they are of average risk. We sought to identify risk factors for CRC in this population.MethodsWe compared sociodemographic and medical characteristics of patients who received a diagnosis of CRC at an age of 18-49 years (early-onset) with patients who received a diagnosis of CRC at an age of 50 years or older (late-onset) and with age-matched, cancer-free individuals (controls) at a tertiary academic hospital. We collected data from all adult patients with a diagnosis of CRC from January 1, 2011 through April 3, 2017 from electronic health records. Associations with risk factors were assessed using univariable and multivariable logistic regression models.ResultsWe identified 269 patients with early-onset CRC, 2802 with late-onset CRC, and 1122 controls. Compared with controls, patients with early-onset CRC were more likely to be male (odds ratio [OR], 1.87; 95% CI, 1.39-2.51), have inflammatory bowel disease (IBD) (3% vs 0.4% for controls; univariable P < .01), and have a family history of CRC (OR, 8.61; CI, 4.83-15.75). Prevalence values of well-established modifiable CRC risk factors, including obesity, smoking, and diabetes, were similar. Compared to patients with late-onset CRC, patients with early-onset CRC were more likely to be male (OR, 1.44; 95% CI, 1.11-1.87), black (OR, 1.73; 95% CI, 1.08-2.65) or Asian (OR, 2.60; 95% CI, 1.57-4.15), and have IBD (OR, 2.97; 95% CI, 1.16-6.63) or a family history of CRC (OR, 2.87; 95% CI, 1.89-4.25). Sensitivity analyses excluding IBD and family history of CRC showed comparable results. Early-onset CRC was more likely than late-onset disease to be detected in the left colon or rectum (75% vs 59%, P = .02) and at a late stage of tumor development (77% vs 62%, P = .01).ConclusionsIn a retrospective study of patients with early-onset CRC vs late-onset CRC or no cancer, we identified non-modifiable risk factors, including sex, race, IBD, and family history of CRC, to be associated with early-onset CRC.