Several individual studies have suggested that autosomal CpG methylation differs by sex both in terms of individual CpG sites and global autosomal CpG methylation. However, these findings have been ...inconsistent and plagued by spurious associations due to the cross reactivity of CpG probes on commercial microarrays. We collectively analysed 76 published studies (n = 6,795) for sex-associated differences in both autosomal and sex chromosome CpG sites.
Overall autosomal methylation profiles varied substantially by study, and we encountered substantial batch effects. We accounted for these by conducting random effects meta-analysis for individual autosomal CpG methylation associations. After excluding non-specific probes, we found 184 autosomal CpG sites differentially methylated by sex after correction for multiple testing. In line with previous studies, average beta differences were small. Many of the most significantly associated CpG probes were new. Of note was differential CpG methylation in the promoters of genes thought to be involved in spermatogenesis and male fertility, such as SLC9A2, SPESP1, CRISP2, and NUPL1. Pathway analysis revealed overrepresentation of genes differentially methylated by sex in several broad Gene Ontology biological processes, including RNA splicing and DNA repair.
This study represents a comprehensive analysis of sex-specific methylation patterns. We demonstrate the existence of sex-specific methylation profiles and report a large number of novel DNA methylation differences in autosomal CpG sites between sexes.
To describe the choroidal thickness (ChT) in a large sample of young adults with the aim of establishing a normative ChT profile reference in this demographic cohort and explore its association with ...best-corrected visual acuity (BCVA).
Cross-sectional study.
From a single center, 741 young adults (19-30 years of age, 49% male) were recruited to undergo a comprehensive ophthalmic examination, including BCVA measurement, post-cycloplegic autorefraction, ocular biometry, tonometry, and spectral-domain optical coherence tomography (SD-OCT) imaging. The enhanced depth imaging mode on the SD-OCT was used. The main outcome measure was the central macular ChT (0.5-mm radius around the fovea). The ChTs at the inner (between 0.5-mm and 1.5-mm radius) and outer macular rings (between 1.5-mm and 2.5-mm radius) were also measured.
The median central macular ChT was 370 μm (interquartile range 312-406 μm). The choroid was thickest at the superior-inner, inferior-inner, and central macular regions (370-373 μm) and thinnest nasally at the outer macular region (median 256 μm). Decreased central macular ChT was associated with younger age, female sex, nonwhite ethnicities, and myopia (P ≤ .013). There was a significant association between better BCVA and increased central macular ChT (P < .001), after adjusting for age, sex, ethnicity, and ocular measures. His relationship was only apparent in eyes with central macular ChTs <300 μm (P = .019) and absent in eyes with ChTs >300 μm.
The central ChT of young adults was 370 μm. There was a significant association between worse BCVA and thinner choroids below a threshold of 300 μm, raising the possibility that ChT could be predictive of visual function.
•Choroidal thickness in young adults is predictive of best-corrected visual acuity•Thicker choroid is associated with older age, at least up to 30 years old•Female sex and nonwhite ethnicity are associated with thinner choroids
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a ...genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
BackgroundConjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting conjunctival damage related to ultraviolet radiation exposure. In cross-sectional studies, CUVAF area is ...positively associated with self-reported time spent outdoors and pterygium and negatively associated with myopia; however, longitudinal studies are scarce.AimsTo use a novel deep learning-based tool to assess 8-year change in CUVAF area in young adults, investigate factors associated with this change and identify the number of new onset pterygia.MethodsA deep learning-based CUVAF tool was developed to measure CUVAF area. CUVAF area and pterygium status were assessed at three study visits: baseline (participants were approximately 20 years old) and at 7-year and 8-year follow-ups. Participants self-reported sun protection behaviours and ocular history.ResultsCUVAF data were available for 1497 participants from at least one study visit; 633 (43%) participants had complete CUVAF data. Mean CUVAF areas at baseline and the 7-year and 8-year follow-ups were 48.4, 39.3 and 37.7 mm2, respectively. There was a decrease in mean CUVAF area over time (change in total CUVAF area=−0.96 mm2 per year (95% CI: −1.07 to –0.86)). For participants who wore sunglasses ≥1/2 of the time, CUVAF area decreased by an additional −0.42 mm2 per year (95% CI: −0.72 to –0.12) on average. Fourteen (1.5%) participants developed a pterygium.ConclusionsIn this young adult cohort, CUVAF area declined over an 8-year period. Wearing sunglasses was associated with a faster reduction in CUVAF area. Deep learning-based models can assist in accurate and efficient measurement of CUVAF area.
Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that ...identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.
To investigate the association between serum vitamin D levels and myopia in young adults.
A total of 946 individuals participating in the 20-year follow-up of the Western Australian Pregnancy Cohort ...(Raine) Study were included in this study. Ethnicity, parental myopia, and education status were ascertained by self-reported questionnaire. A comprehensive ophthalmic examination was performed, including postcycloplegic autorefraction and conjunctival UV autofluorescence photography. Serum 25-hydroxyvitamin D₃ (25(OH)D₃) concentrations were determined using mass spectrometry. The association between serum 25(OH)D₃ concentrations and prevalent myopia was determined using multivariable logistic regression. Myopia was defined as mean spherical equivalent ≤ -0.5 diopters.
Of the 946 participants, 221 (23.4%) had myopia (n = 725 nonmyopic). Myopic subjects had lower serum 25(OH)D₃ concentrations compared to nonmyopic participants (median 67.6 vs. 72.5 nmol, P = 0.003). In univariable analysis, lower serum 25(OH)D₃ concentration was associated with higher risk of having myopia (odds ratio OR for <50 vs. ≥50 nmol/L: 2.63; confidence interval 95% CI 1.71-4.05; P < 0.001). This association persisted after adjustment for potential confounders, including age, sex, ethnicity, parental myopia, education status, and ocular sun-exposure biomarker score (adjusted OR 2.07; 95% CI 1.29-3.32; P = 0.002).
Myopic participants had significantly lower 25(OH)D₃ concentrations. The prevalence of myopia was significantly higher in individuals with vitamin D deficiency compared to the individuals with sufficient levels. Longitudinal studies are warranted to investigate whether higher serum 25(OH)D₃ concentration is protective against myopia or whether it is acting as a proxy for some other biologically effective consequence of sun exposure.
Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of ...almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations. These results confirm the polygenic nature of complex phenotypes and improve our understanding of melanin pigment metabolism in humans.
PRéCIS:This study found an association between thinner superotemporal retinal nerve fiber layer (RNFL) and obstructive sleep apnea (OSA). However, the lack of association of sleep apnea with other ...disc measures does not support a link with glaucoma.
AIM:Previous findings on the link between OSA and increased glaucoma risk have been inconsistent. In a community-based study of middle-aged and older adults, we explored for differences in optic disc measures that may resemble preclinical glaucomatous changes in relation to OSA status and severity.
METHODS:A total of 865 participants (46 to 67 y; 45% male) underwent an at-home sleep study during which their apnea-hypopnea index (AHI) and sleep oxygen saturation level were measured. Participants were determined to have no OSA (AHI<5 events/h), mild (AHI 5 to 15), moderate (AHI 16 to 30), or severe OSA (AHI>30). At a 6-year follow-up visit, the optic discs of both eyes were imaged using spectral domain optic coherence tomography to measure the Bruch membrane opening-minimum rim widths and RNFL thicknesses.
RESULTS:On the basis of the AHI, 411 participants (48%) had OSA, of whom 92 (11% of total sample) and 26 (3%) had moderate and severe OSA, respectively. In the multivariate analysis, participants with severe OSA had thinner RNFL superotemporally than those without OSA or with mild OSA (P<0.001 and 0.001, respectively). In addition, superotemporal RNFL was inversely associated with AHI (P=0.004) and sleep time with oxygen saturation level <90% (P=0.005). There was no association between OSA measures and Bruch membrane opening-minimum rim widths.
CONCLUSIONS:Our findings do not provide strong evidence of a link between measures of OSA and the optic disc. However, the association between increased OSA severity and thinner superotemporal RNFL has been reported consistently in previous studies and thus warrants further evaluation.
Purpose To determine the association between ocular sun exposure measured by conjunctival ultraviolet (UV) autofluorescence and myopic refractive error in young adults. Design Cross-sectional study. ...Methods setting : Population-based cohort in Western Australia. study population : Total of 1344 mostly white subjects aged 19–22 years in the Western Australian Pregnancy Cohort (Raine) Eye Health Study. observation procedures : Cycloplegic autorefraction, conjunctival ultraviolet autofluorescence photography, participant questionnaire. main outcome measures : Prevalence of myopic refractive error (spherical equivalent less than −0.50 diopters) and area of conjunctival ultraviolet autofluorescence in mm2. Results There was an inverse relationship between myopic refractive error and ocular sun exposure, with more than double the prevalence of myopia in the lowest quartile of conjunctival autofluorescence than the highest quartile (33.0% vs 15.6%). Median area of autofluorescence was significantly lower in myopic than in nonmyopic subjects (31.9 mm2 vs 47.9 mm2 , P < .001). These differences remained significant after adjustment for age, sex, parental history of myopia, and subject level of education. The use of corrective lenses did not explain the lower conjunctival autofluorescence observed in myopic subjects. Conclusions In this young adult population, myopic refractive error was inversely associated with objectively measured ocular sun exposure, even after adjustment for potential confounders. This further supports the inverse association between outdoor activity and myopia.
To examine the impact of sun exposure on human health, accurate measures of past sun exposure are required. We investigated how young adults' recall of childhood sun-related behaviours compares with ...parent-reported measures collected during childhood. The Kidskin-Young Adult Myopia Study (KYAMS) is a follow-up of the Kidskin Study, a sun-protection intervention study conducted from 1995-2001. KYAMS participants, aged 25-30 years, reported time in sun, and use of hats and sunscreen, for each year from ages 5-26 years (n = 244). Using weighted kappa, we assessed agreement between these data and corresponding variables derived from the Kidskin Study parent questionnaires completed when KYAMS participants were aged 6-12 years. Ordinal logistic regression was used to test the association between self-reported sun-behaviours and corresponding parent-reported data. We found slight agreement between self-reported and parent-reported data for all sun-behaviour measures except hat use at 12 years. KYAMS recall of time in sun at 8-12 years was not associated with Kidskin Study parent-reported responses after adjustment for current time in sun. Recall of higher hat and sunscreen use was associated with higher parent-reported hat and sunscreen use (ORhat = 1.37, 95% CI: 1.16, 1.62; ORsunscreen = 1.23, 95% CI: 1.03, 1.48). However, KYAMS self-reported data were unable to predict corresponding parent-reported responses. Group data from retrospective recall of sun-related behaviours may be of limited value in studying the relationship between sun exposure and health outcomes; however, individual data are likely of little use.
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