rs10991417 (ABCA1): Tissue Gene Expression Variant
Key takeaways
- The ALT allele of rs10991417 is linked to reduced expression of a nearby gene across 8 different body tissues
- Expression reductions are seen in sigmoid colon, pituitary gland, aorta, tibial nerve, lower leg skin, tibial artery, subcutaneous fat, and skeletal muscle
- GTEx v11 data from 953 donors shows p-values below 5e-10 across all 8 tissue associations, all passing FDR correction
- A large UK Biobank GWAS of body-shape traits covered this genomic region in over 400,000 individuals
Key takeaways
- The ALT allele of rs10991417 is linked to reduced expression of a nearby gene across 8 different body tissues
- Expression reductions are seen in sigmoid colon, pituitary gland, aorta, tibial nerve, lower leg skin, tibial artery, subcutaneous fat, and skeletal muscle
- GTEx v11 data from 953 donors shows p-values below 5e-10 across all 8 tissue associations, all passing FDR correction
- A large UK Biobank GWAS of body-shape traits covered this genomic region in over 400,000 individuals
What the research says GTEx v11 cis-eQTL data (measuring how a nearby genetic variant influences a gene's expression levels) from 953 donors shows the ALT allele at rs10991417 is associated with reduced expression of gene ENSG00000226334 across eight tissues, with the strongest signal in sigmoid colon and pituitary gland GTEx Portal. A genome-wide association study of allometric body-shape indices, specifically A Body Shape Index (ABSI, a waist-size measure adjusted to be independent of height and general adiposity) and Hip Index (HI), was conducted in 219,872 women and 186,825 men with white British ancestry from UK Biobank using Bayesian linear mixed-models (BOLT-LMM, a statistical approach that accounts for genetic relatedness across a large sample).
Reported associations
- Gene expression (ENSG00000226334), sigmoid colon: ALT allele linked to reduced expression; effect size slope -0.48 per ALT allele (p=4.9e-13) GTEx Portal
- Gene expression (ENSG00000226334), pituitary gland: ALT allele linked to reduced expression; slope -0.46 (p=6.1e-10) GTEx Portal
- Gene expression (ENSG00000226334), aorta: ALT allele linked to reduced expression; slope -0.35 (p=9.6e-10) GTEx Portal
- Gene expression (ENSG00000226334), tibial nerve: ALT allele linked to reduced expression; slope -0.34 (p=4.0e-12) GTEx Portal
- Gene expression (ENSG00000226334), lower leg skin (sun-exposed): ALT allele linked to reduced expression; slope -0.33 (p=4.3e-11) GTEx Portal
- Gene expression (ENSG00000226334), tibial artery: ALT allele linked to reduced expression; slope -0.32 (p=1.2e-10) GTEx Portal
- Gene expression (ENSG00000226334), subcutaneous adipose tissue: ALT allele linked to reduced expression; slope -0.32 (p=4.8e-12) GTEx Portal
- Gene expression (ENSG00000226334), skeletal muscle: ALT allele linked to reduced expression; slope -0.31 (p=1.0e-11) GTEx Portal
Evidence quality The GTEx v11 eQTL dataset from 953 donors demonstrates consistent, statistically significant reduced expression of gene ENSG00000226334 across all 8 tested tissues, with p-values ranging from 1.2e-10 to 4.9e-13, all passing FDR correction (a false discovery rate threshold meaning fewer than 5% of these signals are expected by chance) GTEx Portal. The uniformity of effect direction across 8 anatomically diverse tissue types supports a cis-regulatory role at this locus; no conflicting directional findings are present among the provided sources. These eQTL findings reflect a potential regulatory mechanism and do not directly indicate clinical outcomes. The GWAS of allometric body-shape indices covered over 400,000 UK Biobank participants using validated statistical methods; the available study text does not report specific effect sizes or p-values for rs10991417 in that body-shape analysis, and no independent replication study for this variant is included among the provided sources.
Tissue-specific expression effects
- ENSG00000226334: The ALT allele is associated with reduced expression in sigmoid colon, pituitary gland, aorta, tibial nerve, sun-exposed lower leg skin, tibial artery, subcutaneous adipose tissue, and skeletal muscle; all 8 tissues show the same direction of effect GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10991417?
rs10991417 is a single nucleotide polymorphism, a single-letter variation in DNA, located in or near the ABCA1 gene. The ALT allele of this variant is consistently associated with reduced expression of a nearby gene across multiple tissue types in GTEx eQTL data from 953 donors.
Which tissues are affected by rs10991417?
GTEx v11 data shows the ALT allele reduces expression of gene ENSG00000226334 in sigmoid colon, pituitary gland, aorta, tibial nerve, lower leg skin, tibial artery, subcutaneous fat, and skeletal muscle. All 8 tissues show reduced rather than increased expression, with p-values all below 5e-10.
What is an eQTL variant?
An eQTL (expression quantitative trait locus) is a genetic variant associated with differences in how much RNA a nearby gene produces in certain cell types. rs10991417 acts as a cis-eQTL, meaning the ALT allele is correlated with lower amounts of a neighboring gene's RNA in the tested tissues.
Is rs10991417 linked to body shape?
This genomic region was included in a large UK Biobank genome-wide association study of allometric body-shape indices, specifically A Body Shape Index and Hip Index, covering over 400,000 individuals. The available study text does not report specific association statistics for rs10991417 in that body-shape analysis.
How reliable is the evidence for rs10991417 expression effects?
GTEx v11 data from 953 donors shows statistically significant reduced expression across all 8 tested tissues, with p-values ranging from 1.2e-10 to 4.9e-13, all passing FDR correction. The consistency of direction across 8 independent tissue types strengthens confidence in the cis-regulatory signal, though eQTL findings describe mechanism rather than direct health outcomes.