Anthropometric traits, intraocular pressure, and glaucoma in the Canadian Longitudinal Study on Aging: a sex-specific Mendelian randomization study

Purpose Investigate potential causal relationships of body mass index (BMI) and waist-to-hip ratio (WHR) with intraocular pressure (IOP) and glaucoma using sex-specific Mendelian randomization (MR). Methods Cross-sectional analyses were performed using baseline data on 22,902 study participants from the Canadian Longitudinal Study on Aging (CLSA). Sex-specific associations of body mass index and WHR with corneal-compensated intraocular pressure and glaucoma were examined using multivariable linear and logistic regression. One-sample and two-sample Mendelian randomization analyses were conducted to assess potential causality. Results BMI was positively associated with IOP for both males (β = 0.125 per standard deviation (SD), 95% confidence interval (CI) [0.049, 0.200]) and females (β = 0.235 per SD, 95% CI [0.164, 0.307]). WHR was significantly associated with IOP for females (β = 0.098 per SD, 95% CI [0.025, 0.170]), but not males ( P -value = 0.463). BMI and WHR were not significantly associated with glaucoma for either sex ( P -value ≥0.2). For the one-sample MR analyses, the effect of genetically predicted BMI on IOP in males was borderline significant (β = 0.434 per SD, 95% confidence interval (CI) [0.005, 0.874], P -value = 0.053). The two-sample MR analyses found evidence of genetically predicted BMI being associated with IOP in females (Weighted Median: β = 0.694 per SD, 95% CI [0.127, 1.260], P -value = 0.016). MR results were not significant for WHR ( P -value >0.05). Conclusion Sex-specific MR found suggestive evidence that BMI (general adiposity) might be causally linked to IOP.