PUBLIC HEALTH / RESEARCH PAPER
Visual impairment and frailty: insight from genetic correlation and Mendelian randomization
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1
2. Chengdu University of Traditional Chinese Medicine, China
2
1. Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, China
Submission date: 2024-07-30
Final revision date: 2025-01-22
Acceptance date: 2025-02-04
Online publication date: 2025-04-20
Corresponding author
Tianshu Hou
1. Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, No.18, Wanxiang North Road, Gaoxin District, Cheng, 610095, Chengdu,Sichuan,China, China
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ABSTRACT
Introduction:
Visual impairment (VI) is associated with frailty in observational studies, but whether this relationship is causal remains uncertain. This study aimed to investigate the genetic correlation and causal associations between genetically predicted VI and frailty using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC).
Material and methods:
Genome-wide association studies provided summary data for VI subtypes (glaucoma, cataracts, diabetic retinopathy, age-related macular degeneration, hypermetropia, myopia) and frailty measures (Frailty Index (FI) and Fried Frailty Score (FFS)). LDSC was used to estimate genetic correlations, and MR was conducted using inverse-variance weighted (IVW) as the primary method, supplemented by MR-Egger and weighted median. Sensitivity analyses, including Radial MR, Cochran's Q test, MR-Egger intercept, and MR-PRESSO, assessed pleiotropy and heterogeneity.
Results:
Significant genetic correlations were found between VI, cataracts, age-related macular degeneration, and frailty. Suggestive correlations were identified between myopia and FI. MR analysis showed increased FI and FFS risks with other cataracts (FI: P = 0.0324; FFS: P = 0.027) and diabetic retinopathy (FI: P < 0.001; FFS: P = 0.0119). Visual disturbances were linked to increased FI risk (P = 0.0101), while age-related macular degeneration elevated FFS risk (P = 0.0251). Reverse analysis revealed frailty also increased susceptibility to VI. No causal relationships were found for other eye diseases, and analyses showed no evidence of pleiotropy or heterogeneity.
Conclusions:
This study highlights significant genetic links and bidirectional causal relationships between VI and frailty. Future research should include multiethnic populations and larger datasets to further explore these mechanisms.