rs11858077 (CARMAL): Vascular Gene Expression Variant
Key takeaways
- The ALT allele of rs11858077 reduces expression of CARMAL in eight tissues, with the strongest effect in the aorta
- All effects point in the same direction: reduced CARMAL expression wherever the gene is active
- Cardiovascular tissues (aorta, coronary artery, tibial artery) show among the most statistically significant effects
- This variant was identified in large GWAS studies covering blood cell phenotypes and thousands of traits across diverse populations
Key takeaways
- The ALT allele of rs11858077 reduces expression of CARMAL in eight tissues, with the strongest effect in the aorta
- All effects point in the same direction: reduced CARMAL expression wherever it is measured
- Cardiovascular tissues (aorta, coronary artery, tibial artery) show among the most statistically significant effects
- This variant was identified in large genome-wide association studies covering blood cell phenotypes and thousands of traits across diverse populations
What the research says rs11858077 appears in two large genome-wide association studies (GWAS - an approach that screens millions of genetic variants across a population for associations with traits): the VA Million Veteran Program (MVP) analysis of 2068 traits in 635,969 participants from diverse US populations, and a study of 29 blood cell phenotypes in 563,085 European-ancestry participants. Tissue-specific expression data from GTEx v11 (953 donors) documents that the ALT allele at this locus consistently reduces expression of CARMAL, the gene it is annotated to, with the most significant signal in the aorta (slope -0.42, p=4.9e-28) and similar effects across seven additional tissues GTEx Portal.
Reported associations
- CARMAL expression - Aorta: ALT allele associated with reduced CARMAL expression (slope -0.42, p=4.9e-28, n=953 donors) GTEx Portal
- CARMAL expression - Skin (sun-exposed, lower leg): ALT allele associated with reduced CARMAL expression (slope -0.30, p=5.1e-16) GTEx Portal
- CARMAL expression - Visceral adipose tissue (omentum): ALT allele associated with reduced CARMAL expression (slope -0.29, p=9.6e-17) GTEx Portal
- CARMAL expression - Subcutaneous adipose tissue: ALT allele associated with reduced CARMAL expression (slope -0.29, p=5.7e-23) GTEx Portal
- CARMAL expression - Thyroid: ALT allele associated with reduced CARMAL expression (slope -0.28, p=3.2e-12) GTEx Portal
- CARMAL expression - Tibial nerve: ALT allele associated with reduced CARMAL expression (slope -0.26, p=1.2e-13) GTEx Portal
- CARMAL expression - Tibial artery: ALT allele associated with reduced CARMAL expression (slope -0.26, p=5.0e-23) GTEx Portal
- CARMAL expression - Coronary artery: ALT allele associated with reduced CARMAL expression (slope -0.26, p=1.1e-10) GTEx Portal
Evidence quality The eQTL (expression quantitative trait locus - a variant that predicts the level of a nearby gene's expression) evidence from GTEx v11 is based on 953 donors and is statistically robust across all eight tissues, with p-values ranging from 4.9e-28 in the aorta to 3.2e-12 in the thyroid, all at FDR below 0.05. The consistent negative direction of effect across every tested tissue - spanning cardiovascular, metabolic, neural, and skin compartments - strengthens confidence in the signal. The two GWAS studies referenced are large and well-powered, covering 563,085 to 635,969 participants from diverse populations, but specific effect sizes and p-values for rs11858077 in those studies are not present in the available study excerpts. No conflicting findings are reported in the provided data, and the downstream biological and clinical consequences of reduced CARMAL expression remain incompletely characterized.
Tissue-specific expression effects
- CARMAL: The ALT allele is associated with reduced expression in all eight tissues tested in GTEx v11 - most strongly in the aorta, with additional reduced expression in sun-exposed skin, visceral and subcutaneous adipose tissue, thyroid, tibial nerve, tibial artery, and coronary artery, all at FDR below 0.05 GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does rs11858077 do to gene expression?
The ALT allele of rs11858077 reduces expression of CARMAL in at least eight tissues including the aorta, coronary arteries, adipose fat deposits, thyroid, tibial nerve, and skin. This kind of variant is called an eQTL, short for expression quantitative trait locus.
What is the CARMAL gene?
CARMAL is a gene expressed across cardiovascular tissues such as the aorta and coronary arteries, as well as adipose tissue, thyroid, tibial nerve, and skin. Its precise biological role is under active investigation.
Which tissue shows the biggest CARMAL expression effect for rs11858077?
The aorta shows the strongest effect. In GTEx v11 data from 953 donors, the ALT allele reduces CARMAL expression with a slope of -0.42 in log2-normalized units at a p-value of 4.9e-28.
Is rs11858077 linked to heart disease?
The available studies do not directly establish a link to heart disease. While the variant reduces CARMAL expression in cardiovascular tissues, the clinical significance of this expression change has not been demonstrated in the provided data.
What large studies include rs11858077?
The variant appears in the VA Million Veteran Program GWAS covering 2068 traits in 635,969 diverse US participants, and in a study of 29 blood cell phenotypes across 563,085 European-ancestry participants.