rs11921770 (LINC01266): AMD and VLDL Lipoprotein Risk

Key takeaways

• This variant is studied in relation to circulating blood lipoprotein levels and age-related macular degeneration (AMD) risk.
• A 2024 UK Biobank analysis of 72,376 participants found depletion of very small VLDL particles is likely causally linked to AMD.
• 84 of 325 blood metabolites tested were significantly associated with AMD, with lipoprotein subclasses comprising 39% of those hits.
• Evidence comes from a single large study using Mendelian randomization; independent replication has not yet been reported.

What the research says A 2024 analysis of 72,376 UK Biobank participants (1,353 AMD cases, 71,023 non-AMD controls) tested 325 blood metabolites for association with AMD and identified 84 significant associations (false discovery rate-adjusted p < 0.05; FDR is a statistical correction that limits the expected share of false positives among significant results), of which 39% involved lipoprotein subclasses. Using two-sample Mendelian randomization - a method that uses genetic variants as proxies to test whether a metabolite causally affects a disease rather than merely correlating with it - 19 metabolites showed likely causal roles in AMD, with 6 belonging to the very small VLDL (very low-density lipoprotein) subclass and one representing the phospholipid-to-total-lipid ratio in medium VLDL. The authors conclude that depletion of circulating very small VLDL is likely causal for AMD.

Reported associations

• Age-related macular degeneration risk: Depletion of circulating very small VLDL particles was identified as likely causally associated with AMD in a Mendelian randomization study of 72,376 UK Biobank participants (1,353 AMD cases, 71,023 controls).
• Circulating lipoprotein profile: Large and extra-large HDL (high-density lipoprotein) subclasses were elevated in AMD patients; VLDL, amino acids, and citrate were reduced in AMD cases relative to controls.
• Very small VLDL subclass levels: Six specific metabolites within the very small VLDL lipoprotein subclass, plus the phospholipid-to-total-lipid ratio in medium VLDL, were among 19 metabolites with likely causal effects on AMD.
• AMD risk prediction: A machine learning risk model built from metabolites, age, and sex identified age as the primary predictor of AMD risk, with metabolites providing a smaller additional contribution.

Evidence quality Evidence derives from a single large study (Farashi et al., Ophthalmology Science, 2024) using a multi-tiered design: observational metabolite analysis in 72,376 UK Biobank donors, genome-wide association studies (GWAS) for 325 metabolites in 98,316 European participants, and two-sample Mendelian randomization to assess causality. The Mendelian randomization approach provides stronger causal inference than observational methods alone. However, findings from a single cohort require independent replication before strong conclusions can be drawn. No conflicting studies were provided. The study did not report specific p-values for individual variant-level associations in the text available for this entry.

Lifestyle considerations No lifestyle considerations on file for this variant.