Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study

Abstract

Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association study (GWAS) data of Biobank Japan (BBJ) and the meta-analysis data from BBJ and UK Biobank (UKB) were used as instrumental variables (IVs). The GWAS dataset for glaucoma was extracted from the meta-analysis data (n = 240,302) of Genetic Epidemiology Research in Adult Health and Aging and UKB. The casual estimates were assessed with a two-sample Mendelian randomisation (MR) test using the inverse-variance-weighted (IVW) method, weighted median method, MR–Egger method, and MR-Pleiotropy Residual Sum and Outlier test. The IVW method revealed a significant causal association between iritis and glaucoma using IVs (p < 5.0 × 10−8) from the East Asian population (n = 2) (odds ratio [OR] = 1.01, p = 0.017), a significant association between iritis exposures (p < 5.0 × 10−8) in the multi-ethnic population (n = 11) (OR = 1.04, p = 0.001), and a significant causal association between uveitis exposures (n = 10 with p < 5.0 × 10−8) and glaucoma in the multi-ethnic population (OR = 1.04, p = 0.001). Iritis and uveitis had causal effects on glaucoma risk based on IVs from the multi-ethnic population. These findings imply that the current classifications of uveitic glaucoma and open-angle glaucoma overlap, indicating the need for further investigating these complex relationships.

Potential Causal Association between Elevated Gamma-Glutamyl Transferase Level and Stroke: A Two-Sample Mendelian Randomization Study

“…The MR method uses genetic variations associated with a particular exposure to examine how changing that exposure affects disease risk. The advantages of MR research are that, when a set of genomic data and clinical information are available, the design is cross-sectional, but it can be rigorously verified by randomization, as in a prospective study [53,54]. In addition, unlike animal experiments, the MR method reduces the burden of random verification on humans and can demonstrate causality without putting participants at risk [55].…”

Update on Diagnosis and Treatment of Uveitic Glaucoma

“…There are also poorly studied mechanisms involved. For example, an attempt to identify a causal association between uveitis and glaucoma in the general population has disclosed a possible genetic link [ 28 ].…”

Causal Associations of Glaucoma and Age-Related Macular Degeneration with Cataract: A Bidirectional Two-Sample Mendelian Randomisation Study

“…Mendelian randomisation (MR) is a genetic epidemiological approach, which employs genetic variants associated with risk factors as instrumental variables (IVs) to evaluate their causal impact on medical conditions [20,21]. Recently, several studies using MR techniques have shown the potential causal effects of several risk factors on ophthalmic diseases, such as POAG, AMD, cataract, uveitis, and myopia [22][23][24][25][26]. It is meaningful to investigate the association of cataract with glaucoma and AMD, as these are eye diseases, which share risk factors with geriatric diseases.…”