Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights.

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion and trabecular meshwork changes, resulting in increased intraocular pressure and potential glaucomatous optic neuropathy. This review summarizes recent progress in PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) and susceptibility loci identified from genome-wide association studies (GSAP and GRM5/TYR). Areas for future research are also identified, especially the development of efficient model systems. While substantial strides have been made in understanding the genetics of PDS/PG, our review identifies key gaps and outlines the future directions necessary for further advancing this important field of ocular genetics.

Lack of Association between LOXL1 Variants and Pigment Dispersion Syndrome/Pigmentary Glaucoma: A Meta-Analysis.

The phenotypic similarities between exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and pigment dispersion syndrome (PDS)/pigmentary glaucoma (PG), particularly their association with material deposition in the eye's anterior segment, have prompted investigations into genetic commonalities. This study focuses on the LOXL1 gene, conducting a comprehensive meta-analysis of three candidate gene association studies. We analyzed three single nucleotide polymorphisms (SNPs) of LOXL1: rs1048661, rs3825942, and rs2165241. Our results reveal nominal significance for the exonic SNPs rs1048661 and rs3825942 (p ≤ 0.01), but show no significant association for the intronic SNP rs2165241 (p = 0.83) with PDS/PG. There was homogeneity across study cohorts (I2 = 0), and sensitivity analyses and funnel plots confirmed a lower likelihood of bias in our findings. The lack of a statistically significant association between LOXL1 variants and PDS/PG at p < 0.05 was attributable to the insufficient statistical power of the pooled data, which ranged from 5% to 37% for the three SNPs. This study suggests no association between LOXL1 variants and PDS/PG. Further validation and exploration of XFS/XFG-associated genes in larger and more diverse cohorts would be helpful to determine the genetic correlation or distinctiveness between these conditions.

Multilevel Risk Factors for Sleep-Disordered Breathing-Related Symptom Burden in an Urban Pediatric Community-Based Sample.

BACKGROUND: Pediatric sleep-disordered breathing (SDB) disproportionately affects children with low socioeconomic status (SES). The multilevel risk factors that drive these associations are not well understood. RESEARCH QUESTION: What are the associations between SDB risk factors, including individual health conditions (obesity, asthma, and allergies), household SES (maternal education), indoor exposures (environmental tobacco smoke [ETS] and pests), and neighborhood characteristics (neighborhood disadvantage), and pediatric SDB symptoms? STUDY DESIGN AND METHODS: Cross-sectional analyses were performed on 303 children (aged 6-12 years) enrolled in the Environmental Assessment of Sleep Youth study from 2018 to 2022. Exposures were determined by caregiver reports, assays of measured settled dust from the child's bedroom, and neighborhood-level Census data (deriving the Childhood Opportunity Index to characterize neighborhood disadvantage). The primary outcome was the SDB-related symptom burden assessed by the OSA-18 questionnaire total score. Using linear regression models, we calculated associations between exposures and SDB-related symptom burden, adjusting for sociodemographic factors, then health conditions, indoor environment, and neighborhood factors. RESULTS: The sample included 303 children (39% Hispanic, Latino, Latina, or Spanish origin; 30% Black or African American; 22% White; and 11% other). Increasing OSA-18 total scores were associated with low household SES after adjustment for demographic factors, and with asthma, allergies, ETS, pests (mouse, cockroach, and rodents), and an indoor environmental index (sum of the presence of pests and ETS; 0-2) after adjusting for sociodemographic factors. Even after further adjusting for asthma, allergies, and neighborhood disadvantage, ETS and pest exposure were associated with OSA-18 (ETS: ß = 12.80; 95% CI, 7.07-18.53, also adjusted for pest; pest exposure: ß = 3.69; 95% CI, 0.44-6.94, also adjusted for ETS). INTERPRETATION: In addition to associations with ETS, a novel association was observed for indoor pest exposure and SDB symptom burden. Strategies to reduce household exposure to ETS and indoor allergens should be tested as approaches for reducing sleep health disparities.