Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses.

PURPOSE: To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).

DESIGN

Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.

PARTICIPANTS

Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed.

METHODS

Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if P < 0.05 in the primary model and in ≥2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD.

MAIN OUTCOME MEASURES: Causal associations between eGFR and advanced AMD.

RESULTS

In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01-1.25; P = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01-4.08; P = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, P = 2.29 x 10-33 for AMD; P = 2.29 x 10-13 for eGFR).

CONCLUSIONS

Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.