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The Potential Causal Association of Apolipoprotein A and B and Age-Related Macular Degeneration: A Mendelian
Young Lee1,2, Je Hyun Seo1
1Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea.
Background/Objectives:
Research has suggested a potential relationship between apolipoproteins A (ApoA) and B (ApoB) and age-related macular degeneration (AMD). This study explored the potential causal relationship between ApoA/ApoB levels and AMD/AMD subtypes using two-sample Mendelian randomisation (MR).
Methods:
We selected 308 single nucleotide polymorphisms (SNPs) for ApoA and 198 SNPs for ApoB from the UK Biobank data. Summary statistics for AMD were collected from the genome-wide association study of the FinnGen project. We performed two-sample MR to assess the causal effects of ApoA/ApoB on AMD and its subtypes. Potential confounders, including body mass index, C-reactive protein level, and smoking status, were assessed using a multivariable MR analysis.
Results:
ApoA showed a significant causal association with AMD (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.05-1.25, p = 0.003) and was linked to both dry (p = 0.004) and wet (p = 0.025) AMD. ApoB showed a decreasing trend in dry AMD risk (p = 0.074), though not significant, and was not associated with overall or wet AMD. The multivariable MR analysis showed no significant association of ApoA with any AMD subtype (p > 0.05). ApoB decreased dry AMD risk (OR = 0.89, 95% CI = 0.80-0.99, p = 0.039), with trends for overall and wet AMD that were not significant (p = 0.070 and p = 0.091, respectively).
Conclusions:
These findings suggest that ApoB is associated with lower AMD risk, particularly for dry AMD. Further research is needed to clarify lipid biomarker's role as AMD risk factors.
Insights
Apolipoprotein B (ApoB) may reduce the risk of age-related macular degeneration (AMD), especially dry AMD. Apolipoprotein A (ApoA) showed a causal link with AMD, but further research is needed on lipid biomarkers and AMD risk.
Area of Science:
- Ophthalmology
- Genetics
- Biochemistry
Background:
- Apolipoproteins A (ApoA) and B (ApoB) have been potentially linked to age-related macular degeneration (AMD).
- Investigating the causal relationship between these lipid biomarkers and AMD is crucial for understanding disease mechanisms.
Purpose of the Study:
- To explore the potential causal relationship between apolipoprotein A (ApoA) and apolipoprotein B (ApoB) levels and age-related macular degeneration (AMD) and its subtypes.
- To utilize Mendelian randomization (MR) to assess these genetic associations.
Main Methods:
- Two-sample Mendelian randomization (MR) was employed using single nucleotide polymorphisms (SNPs) for ApoA (n=308) and ApoB (n=198) from UK Biobank.
- Genome-wide association study summary statistics for AMD were obtained from the FinnGen project.
- Multivariable MR analysis was conducted to adjust for potential confounders like BMI, C-reactive protein, and smoking status.
Main Results:
- Apolipoprotein A (ApoA) demonstrated a significant causal association with overall AMD (OR=1.14, p=0.003) and its dry (p=0.004) and wet (p=0.025) subtypes.
- Apolipoprotein B (ApoB) was associated with a reduced risk of dry AMD (OR=0.89, p=0.039) in multivariable MR analysis.
- No significant causal associations were found for ApoA with AMD subtypes, nor for ApoB with overall or wet AMD after multivariable adjustment.
Conclusions:
- Apolipoprotein B (ApoB) appears to be associated with a lower risk of age-related macular degeneration (AMD), particularly the dry form.
- The role of lipid biomarkers like ApoA and ApoB as risk factors for AMD requires further investigation.
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