rs12416687 (BORCS7-ASMT): Gene Expression Variant

Key takeaways

• The alternate allele at this locus is strongly linked to reduced AS3MT expression in at least seven tissue types, including arteries, adipose tissue, peripheral nerve, skeletal muscle, and skin.
• The same allele also reduces BORCS7 expression in esophageal mucosa.
• GTEx v11 data from 953 donors shows p-values as low as 1.1e-174 for the AS3MT effects, among the most statistically powerful eQTL signals in the GTEx catalog.
• A large multi-ancestry GWAS of 2068 traits and a blood pressure genetics study both reference this variant, but specific clinical trait results are not available from the provided study summaries.
• Current directly confirmed evidence is at the molecular (gene expression) level; clinical associations remain to be fully established from detailed study data.

What the research says GTEx v11 eQTL (expression quantitative trait locus, meaning a genetic position linked to how much of a gene is produced in cells) analysis of 953 tissue donors shows the alternate allele at rs12416687 is associated with reduced AS3MT expression across seven body tissues, with effect sizes on a log2-normalized scale ranging from -0.83 to -1.17 and p-values from 3.9e-87 to 1.1e-174 across artery, adipose, nerve, fibroblast, muscle, and skin tissue GTEx Portal. The same allele is additionally associated with reduced BORCS7 expression in esophageal mucosa, with an effect size of approximately -0.82 and p = 1.3e-96 GTEx Portal. This locus is catalogued in a large multi-ancestry GWAS spanning 2068 traits and 635,969 diverse participants (Verma et al., Science, 2024) and is referenced in a study of gene-age interactions in blood pressure regulation across 99,241 individuals of European ancestry (Simino et al., American Journal of Human Genetics, 2014), though specific results for rs12416687 are not detailed in the available study summaries.

Reported associations

• AS3MT expression (multiple tissues): The alternate allele is associated with reduced AS3MT expression in artery aorta (effect size -1.17, p = 3.9e-87), artery tibial (effect size -1.13, p = 2.6e-159), adipose subcutaneous (effect size -1.12, p = 2.9e-159), nerve tibial (effect size -1.11, p = 3.5e-159), cultured fibroblasts (effect size -1.06, p = 1.1e-174), skeletal muscle (effect size -0.83, p = 6.4e-125), and sun-exposed lower leg skin (effect size -0.83, p = 6.0e-88); all effect sizes are log2-normalized slopes for the alternate allele GTEx Portal
• BORCS7 expression (esophagus mucosa): The alternate allele is associated with reduced BORCS7 expression in esophageal mucosa (effect size -0.82, p = 1.3e-96); effect size is a log2-normalized slope for the alternate allele GTEx Portal
• Blood pressure regulation: This variant is referenced in a genome-wide study of gene-age interactions for systolic, diastolic, mean arterial, and pulse pressure across 99,241 individuals of European ancestry spanning the CHARGE, Global BPgen, and ICBP Consortia (Simino et al., American Journal of Human Genetics, 2014), which identified 20 genome-wide significant loci; specific results for this variant are not detailed in the available study text
• Multi-trait GWAS associations: This variant falls within the scope of a comprehensive phenome-wide association study cataloguing 26,049 variant-trait associations across 2068 traits in 635,969 diverse VA Million Veteran Program participants (Verma et al., Science, 2024); specific trait associations for this variant are not detailed in the available study summary

Evidence quality The eQTL evidence from GTEx v11 is exceptionally well-powered: data from 953 donors with p-values for AS3MT effects spanning from 3.9e-87 to 1.1e-174 across seven independent tissues, and a BORCS7 effect at p = 1.3e-96 in esophageal mucosa GTEx Portal. The consistency of reduced AS3MT expression across seven independent tissue types strengthens confidence that this reflects a genuine biological signal rather than a statistical artifact. The two large clinical studies referenced, one a 635,969-participant multi-ancestry trait atlas (Verma et al., 2024) and one a 99,241-participant blood pressure investigation (Simino et al., 2014), both represent high-quality, well-powered designs; however, their specific results for this variant are not provided in the available summaries, and clinical trait associations cannot therefore be characterized from the provided data. No conflicting findings are apparent within the available evidence.

Tissue-specific expression effects

• AS3MT: Reduced expression in artery aorta, artery tibial, adipose subcutaneous, nerve tibial, cultured fibroblasts, skeletal muscle, and sun-exposed lower leg skin, all for the alternate allele in GTEx v11 cis-window data (FDR less than 0.05, n = 953 donors), with the largest effect in artery aorta and consistent reduced-expression direction across all seven tissues GTEx Portal
• BORCS7: Reduced expression in esophagus mucosa for the alternate allele in GTEx v11 cis-window data GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.