Expressive

rs10769253 (MYBPC3): ACP2 and MADD eQTL Effects

Key takeaways

  • This variant is linked to lower activity of the ACP2 gene in blood, skin, spleen, and esophagus tissue
  • The same variant is also linked to lower MADD gene activity in brain and heart tissue
  • A 72,376-person study linked low very small VLDL levels to a likely causal role in age-related macular degeneration
  • That study analyzed genetic variants genome-wide but did not specifically name this variant, so a direct link to macular degeneration is unconfirmed

Key takeaways

  • This variant is linked to lower activity of the ACP2 gene in blood, skin, spleen, and esophagus tissue
  • The same variant is also linked to lower MADD gene activity in brain and heart tissue
  • A 72,376-person study linked low very small VLDL levels to a likely causal role in age-related macular degeneration
  • That study analyzed genetic variants genome-wide but did not specifically name this variant, so a direct link to macular degeneration is unconfirmed

What the research says GTEx v11 eQTL (expression quantitative trait locus) data from 953 donors shows rs10769253 is associated with reduced ACP2 expression across 6 tissue types, most strongly in esophagus mucosa, with consistent reductions also in spleen, EBV-transformed lymphocytes, skin, and whole blood (all FDR<0.05) GTEx Portal. This locus is also associated with reduced MADD expression in brain cerebellum and heart atrial appendage GTEx Portal. A separate 3-tiered analysis of 325 blood metabolites in 72,376 UK Biobank donors identified 84 metabolic markers significantly associated with age-related macular degeneration (AMD) at FDR<0.05, with lipoprotein subclasses making up 39% of those markers; Mendelian randomization (a statistical method that uses genetic variants to test causal relationships) identified depletion of circulating very small very low-density lipoprotein (VLDL) particles as likely causal for AMD, though this study analyzed variants genome-wide and did not specifically name rs10769253.

Reported associations

  • ACP2 expression (multi-tissue reduction): reduced expression in esophagus mucosa, spleen, EBV-transformed lymphocytes, sun-exposed skin, non-sun-exposed skin, and whole blood GTEx Portal
  • MADD expression (brain and heart reduction): reduced expression in brain cerebellum and heart atrial appendage GTEx Portal

Evidence quality The most direct evidence for this variant comes from GTEx v11 eQTL data (953 donors, FDR<0.05), which documents consistent ACP2 reductions across 6 diverse tissue types and MADD reductions in 2 tissues. The breadth of ACP2 effects across mucosal, immune, dermal, and blood tissues adds consistency to that association. A UK Biobank metabolite study (72,376 donors) applied Mendelian randomization with FDR-adjusted significance thresholds and identified very small VLDL depletion as likely causal for AMD, representing strong methodology; however, that study analyzed variants genome-wide across 325 metabolites and did not report rs10769253 among its specific named findings. No conflicting findings exist within the provided sources. The clinical significance of the eQTL effects on ACP2 and MADD has not been established by the available materials.

Tissue-specific expression effects

  • ACP2: reduced expression in esophagus mucosa, spleen, EBV-transformed lymphocytes, sun-exposed skin (lower leg), non-sun-exposed skin, and whole blood GTEx Portal
  • MADD: reduced expression in brain cerebellum and heart atrial appendage GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10769253?

rs10769253 is a genetic variant located near the MYBPC3 gene. GTEx data shows it is associated with reduced activity of the ACP2 gene across 6 tissue types including blood, and reduced MADD gene activity in brain and heart.

Which tissues are affected by rs10769253?

GTEx eQTL data shows reduced ACP2 expression in whole blood, spleen, esophagus mucosa, sun-exposed skin, non-sun-exposed skin, and EBV-transformed lymphocytes. Separately, reduced MADD expression is observed in brain cerebellum and heart atrial appendage.

Is rs10769253 linked to age-related macular degeneration?

A 72,376-person UK Biobank study identified depletion of very small VLDL particles as likely causal for age-related macular degeneration. That study analyzed thousands of genetic variants genome-wide but did not specifically name rs10769253, so a direct link is not confirmed by the available evidence.

What is an eQTL and why does it matter for this variant?

An eQTL (expression quantitative trait locus) is a genetic variant associated with changes in gene activity levels in specific tissues. GTEx data identifies rs10769253 as an eQTL that reduces ACP2 and MADD gene activity across multiple tissues.

Why is rs10769253 named after MYBPC3?

Variants are typically named after the nearest gene in the genome. rs10769253 is physically near MYBPC3, but the GTEx eQTL data shows its expression effects are on the neighboring ACP2 and MADD genes rather than on MYBPC3 itself.