Expressive

rs10876405 (SOAT2): Lipid Metabolism Variant

Key takeaways

  • rs10876405 reduces SOAT2 expression across seven tissues, including tibial artery, lung, and testis.
  • Cholesteryl esters are higher in men around age 45-50 than in women of the same age, with differences narrowing as people age.
  • A large lipidomics study of 7,266 people found common genetic variants are not the main driver of sex differences in lipid profiles.
  • Evidence linking this variant to clinical outcomes is limited to gene-expression data from healthy tissue samples.
  • Both SOAT2 and a nearby unnamed gene show reduced activity in tibial nerve tissue in carriers of the alternate allele.

Key takeaways

  • rs10876405 is associated with reduced expression of SOAT2 (sterol O-acyltransferase 2) in at least seven tissues, including lung, tibial artery, and testis.
  • A genome-wide lipidomics study found no major role for common genetic variants in explaining sex differences in plasma lipid profiles.
  • Cholesteryl esters tend to be higher in men around age 45-50 compared with women of the same age, with these differences narrowing or reversing as people age.
  • Both SOAT2 and a nearby gene (ENSG00000309140) show reduced expression in tibial nerve tissue in carriers of the alternate allele.
  • Evidence linking this variant to clinical outcomes is limited to gene-expression data; no large-scale outcome studies are in this record.

What the research says A sex-stratified genome-wide association study of 179 lipid species in 7,266 individuals from the Finnish GeneRISK cohort identified significant sex differences in 141 lipid species, with cholesteryl esters among the species showing higher levels in men aged 45-50 compared with women of the same age; these differences narrowed or reversed with advancing age and were replicated in 2,045 independent participants. That study concluded that common genetic variants do not have a major role in driving sex differences in the lipidome. Separately, GTEx v11 expression data (953 donors, FDR<0.05) identifies rs10876405 as an eQTL - a variant that statistically predicts nearby gene expression levels - for SOAT2 across seven tissues, with the strongest effect sizes observed in testis and tibial nerve GTEx Portal.

Reported associations

  • Lipidome sex differences: A sex-stratified GWAS of 7,266 participants found cholesteryl esters and other lipid species differed significantly between sexes with age-dependent patterns, though common variants were not identified as the primary genetic driver of these differences.
  • SOAT2 expression - testis: The alternate allele is associated with reduced SOAT2 expression in testis tissue (slope -0.61) GTEx Portal.
  • SOAT2 expression - lung: The alternate allele is associated with reduced SOAT2 expression in lung tissue (slope -0.50) GTEx Portal.
  • SOAT2 expression - tibial nerve: The alternate allele is associated with reduced SOAT2 expression in tibial nerve tissue (slope -0.45) GTEx Portal.
  • SOAT2 expression - spleen, thyroid, visceral adipose, tibial artery: Reduced SOAT2 expression is observed in four additional tissues (slopes ranging from -0.35 to -0.44) GTEx Portal.
  • ENSG00000309140 expression - tibial nerve: The alternate allele is associated with reduced expression of ENSG00000309140, a gene near SOAT2, in tibial nerve tissue (slope -0.51) GTEx Portal.

Evidence quality The lipidomics GWAS drew on 7,266 discovery participants with replication in 2,045 individuals, providing reasonable statistical power for lipid trait associations. The study's central finding was that common genetic variants do not explain sex differences in the lipidome, which limits the interpretive weight of individual variants identified in that context. The GTEx eQTL evidence (953 donors, FDR<0.05) consistently shows reduced SOAT2 expression across seven tissues in carriers of the alternate allele, with p-values ranging from 3.0e-20 to 1.3e-28 across tissues, representing strong statistical evidence for a regulatory role at this locus. Critically, eQTL data describes gene-expression patterns in healthy tissue samples, not clinical outcomes; no outcome-based studies linking rs10876405 to cardiovascular events, lipid disorder diagnoses, or related endpoints are present in the provided evidence.

Tissue-specific expression effects

  • SOAT2: Reduced expression in testis, lung, tibial nerve, spleen, thyroid, visceral adipose (omentum), and tibial artery; all seven tissues show lower SOAT2 transcript levels in carriers of the alternate allele, with the largest reductions in testis and tibial nerve GTEx Portal.
  • ENSG00000309140: Reduced expression in tibial nerve tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10876405?

rs10876405 is a genetic variant located near the SOAT2 gene. GTEx gene-expression data from 953 donors shows that the alternate allele at this position is associated with lower SOAT2 expression in seven tissues, including lung, tibial artery, testis, and nerve.

What does the SOAT2 gene do?

SOAT2 stands for sterol O-acyltransferase 2 and is a gene involved in lipid metabolism. Variants in this region have been studied in relation to cholesteryl ester levels, a class of lipids that differ significantly between men and women and change with age.

Is rs10876405 linked to cardiovascular risk?

The provided evidence does not establish a direct link between rs10876405 and cardiovascular disease outcomes. Available data shows reduced SOAT2 gene expression in tissues including tibial artery, and a related lipidomics study noted cholesteryl ester differences between sexes, but no outcome-based clinical associations are on record for this specific variant.

Why do cholesteryl ester levels differ between men and women?

A genome-wide study of 7,266 individuals found cholesteryl esters are generally higher in men around age 45-50 compared with women of the same age, with differences narrowing or reversing with age. The same study found that common genetic variants are not the primary explanation for these sex differences.

What is an eQTL and why does it matter here?

An eQTL (expression quantitative trait locus) is a genetic variant that predicts how much of a gene's messenger RNA is produced in a given tissue. For SOAT2, GTEx data shows that people carrying the alternate allele at rs10876405 consistently produce less SOAT2 transcript across seven different tissues, suggesting this variant has a regulatory role at this locus.