Appetitive Lifestyles and Obesity with Risk of Senile Cataract: An Univariable and Multivariable Mendelian Randomization Study

Abstract

Objective: To estimate the causal effects of appetitive lifestyles (cigarette smoking, alcohol use, coffee consumption) and obesity on risk of senile cataract (SC) using genetically based approaches. Methods: Single nucleotide polymorphisms selected to be instrumental variables for exposures were identified at the level of genome-wide significance (P<5×10-8) from genome-wide association studies. Summary-level genetic statistics for SC was derived from the FinnGen consortium. Univariable and multivariable Mendelian randomization (MR) with inverse-variance weighted (IVW) method as main analysis were performed. Directional pleiotropy and heterogeneity were tested. Results: For univariable MR, genetically determined predisposition to smoking initiation was associated with elevated risk of SC (IVW odds ratio (OR))=1.1241, 95% confidence interval (CI) (CI: 1.0240-1.2339, P=0.0140). Also, genetically predicted higher coffee consumption and body mass index (BMI) was associated with increased risk of SC (IVW OR=1.0050, 95% CI: 1.0012-1.0088, P=0.0101; IVW OR=1.1925, 95% CI: 1.0954-1.2982, P=4.8099×10-5, respectively). For multivariable MR, genetically predicted higher BMI still exerted a causal effect on SC risk (IVW OR=1.1712, 95% CI: 1.0786-1.2717, P<0.001). Nevertheless, the associations of smoking initiation and coffee consumption with SC risk disappeared. No directional pleiotropy was detected in both univariable and multivariable MR. Conclusion: Our findings provide evidence for an adverse effect of higher BMI on SC risk, while no evidence supporting independent causal associations of appetitive lifestyles with SC risk. Improving the management of obesity may serve as a useful strategy protecting against SC.