Systemic inflammatory regulators and age-related macular degeneration: a bidirectional Mendelian randomization study

Area of Science:

• Genetics
• Immunology
• Ophthalmology

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss.
• Systemic inflammation is implicated in AMD pathogenesis, but specific causal links remain unclear.

Purpose of the Study:

• To investigate the causal relationship between systemic inflammation markers and the risk of both wet and dry age-related macular degeneration (AMD).

Main Methods:

• Utilized bidirectional, two-sample Mendelian randomization (MR) analysis with genome-wide association study (GWAS) data for 91 plasma proteins.
• Employed inverse-variance-weighted (IVW) approach and sensitivity analyses including MR-Egger, Weighted median, Weighted mode, MR-PRESSO, and MR-Steiger filtering.

Main Results:

• Identified 16 cytokines associated with AMD risk. Higher levels of fibroblast growth factor 19 (FGF19) and leukemia inhibitory factor receptor (LIFR) were linked to decreased AMD risk.
• Tumor necrosis factor ligand superfamily member 14 (TNFSF14) was associated with increased AMD risk. Specific associations were found for wet AMD (IL-10 receptor subunit alpha) and dry AMD (LIFR, signaling lymphocytic activation molecule).
• Genetic susceptibility to AMD was associated with elevated TNFSF11, IL18R1, and CDCP1 levels, particularly for wet AMD.

Conclusions:

• This study provides novel insights into the etiological role of specific inflammatory proteins in AMD.
• Findings may inform future diagnostic and therapeutic strategies for AMD and its subtypes.