Abstract

We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10–8 were selected as instrument variables. Summary-level data for senile cataract were obtained from the FinnGen consortium (20,157 cases and 154,905 non-cases) and UK Biobank study (6332 cases and 354,862 non-cases). Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. The combined odds ratios were 1.19 (95% confidence interval (CI) 1.09–1.29; p < 0.001) per one standard deviation increase in BMI (~ 4.8 kg/m2), 1.13 (95% CI 1.04–1.23; p = 0.004) per 10 mmHg increase in SBP, 1.06 (95% CI 1.03–1.09; p < 0.001) per one unit increase in log-transformed odds ratio of T2D, and 1.19 (95% CI 1.10–1.29; p < 0.001) per one standard deviation increase in prevalence of smoking initiation. Genetically predicted coffee consumption showed a suggestive association with senile cataract (odds ratio per 50% increase, 1.18, 95% CI 1.00–1.40; p = 0.050). This study suggests causal roles of obesity, T2D, SBP and smoking in senile cataract.

Highlights

  • We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract

  • A genetically predicted one standard deviation increase in BMI corresponded to a combined odds ratio (OR) of 1.19 (95% confidence interval (CI) 1.09, 1.29; p < 0.001)

  • Genetic liability to type 2 diabetes and higher genetically predicted SBP were positively associated with senile cataract in FinnGen and UK Biobank, respectively, and these associations remained directionally consistent in the other data source (Fig. 1)

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Summary

Introduction

We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. Data on the associations of c­ offee[8,9,14] and ­alcohol[10,11,12,14] consumption with senile cataract are conflicting and the causality of these observed associations remains undetermined due to possible limitations, such as residual confounding and other biases, embedded in observational studies. We conducted a MR study to determine the associations of three metabolic traits, including body mass index (BMI), type 2 diabetes and systolic blood pressure (SBP), and three lifestyle factors, including coffee and alcohol consumption and smoking, with risk of senile cataract

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