rs10091374 (LINC03020): cardiac troponin T GWAS
Key takeaways
- rs10091374, located near the NCOA2 gene on chromosome 8q13, was linked to blood levels of highly sensitive cardiac troponin T (hs-cTnT), a protein released during heart muscle injury, in a genome-wide study of over 11,500 adults.
- The association cleared genome-wide significance (p = 9.06 x 10^-9), meeting the standard statistical bar for large-scale genetic discovery.
- The variant reduces expression of LINC03020, a long non-coding RNA, across eight body tissues including liver, brain cortex, and visceral fat, based on GTEx eQTL data.
- Despite the cardiac biomarker link, hs-cTnT-associated variants at this locus were not found to be associated with coronary heart disease in a companion case-control analysis.
- The biological function of LINC03020 is not described in the available source material, limiting what can be concluded from the expression data.
Key takeaways
- rs10091374, located near the NCOA2 gene on chromosome 8q13, was linked to blood levels of highly sensitive cardiac troponin T (hs-cTnT), a protein released during heart muscle injury, in a genome-wide study of over 11,500 adults.
- The association cleared genome-wide significance (p = 9.06 x 10^-9), meeting the standard statistical bar for large-scale genetic discovery.
- The variant reduces expression of LINC03020, a long non-coding RNA, across eight body tissues including liver, brain cortex, and visceral fat, based on GTEx eQTL data.
- Despite the cardiac biomarker link, hs-cTnT-associated variants at this locus were not found to be associated with coronary heart disease in a companion case-control analysis.
- The biological function of LINC03020 is not described in the available source material, limiting what can be concluded from the expression data.
What the research says A genome-wide association meta-analysis of 9,491 European-Americans and 2,053 African-Americans from two large prospective cohort studies, ARIC (Atherosclerosis Risk in Communities) and CHS (Cardiovascular Health Study), identified rs10091374 at chromosome 8q13 near NCOA2 (nuclear receptor coactivator 2, a protein that helps other regulatory proteins control gene activity) as significantly associated with circulating hs-cTnT (highly sensitive cardiac troponin T, a blood marker of heart muscle injury detectable at levels roughly 10 times lower than conventional assays) levels (p = 9.06 x 10^-9, n = 11,544). The same study abstract also assigns the same rsID to a secondary association in the TNNT2 gene at chromosome 1q32 (p = 9.06 x 10^-8), though these loci are on different chromosomes, suggesting a likely reporting inconsistency in the source document. GTEx v11 expression-QTL data from 953 donors further identify rs10091374 as associated with reduced expression of LINC03020, a long intergenic non-coding RNA (a gene that produces RNA but not protein), across eight body tissues GTEx Portal.
Reported associations
- Highly sensitive cardiac troponin T (hs-cTnT) levels: Significant genome-wide association at chromosome 8q13 near NCOA2 (p = 9.06 x 10^-9, n = 11,544 pooled European-American and African-American participants from ARIC and CHS). Variants at this locus were explicitly reported as non-significant for coronary heart disease in a companion case-control analysis.
- LINC03020 expression - visceral adipose tissue (omentum): Alternate allele associated with reduced expression (p = 1.4 x 10^-11), the strongest tissue-level signal for this variant in GTEx v11 GTEx Portal.
- LINC03020 expression - thyroid: Alternate allele associated with reduced expression (p = 1.0 x 10^-10) GTEx Portal.
- LINC03020 expression - pituitary, liver, esophagus muscularis, aorta, brain cortex, cervical spinal cord: Reduced expression across six additional tissues, all reaching study-level significance (FDR < 0.05) in GTEx v11 GTEx Portal.
Evidence quality The hs-cTnT GWAS is based on a meta-analysis of 11,544 participants from two well-established prospective cohort studies using fixed-effect meta-analytic methods. The p-value of 9.06 x 10^-9 surpasses the conventional genome-wide significance threshold of p < 5 x 10^-8. However, no independent replication of the rs10091374 association in external cohorts is described in the provided source material, which is a standard expectation for confirming GWAS findings. A notable internal inconsistency in the abstract assigns the same rsID to loci on two different chromosomes (8q13 near NCOA2 and 1q32 in TNNT2), raising uncertainty about the secondary TNNT2 claim as reported. The hs-cTnT variants were explicitly reported as non-significant for coronary heart disease, indicating the biomarker-level genetic signal does not translate to detected disease risk in these data. GTEx eQTL evidence for LINC03020 draws on 953 donors across eight tissues (all FDR < 0.05), with the most robust signals in visceral adipose tissue (p = 1.4 x 10^-11) and thyroid (p = 1.0 x 10^-10) GTEx Portal. No functional data on LINC03020 are present in the available sources, limiting mechanistic interpretation.
Tissue-specific expression effects
- LINC03020: The alternate allele is associated with reduced expression of this long non-coding RNA across all eight tested tissues - visceral adipose tissue, thyroid, pituitary, liver, esophagus muscularis, aorta, brain cortex, and cervical spinal cord. The direction of effect (lower expression) is consistent across every site, with the largest effects seen in liver and brain cortex and the most statistically significant signal in visceral adipose tissue GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is LINC03020?
LINC03020 is a long intergenic non-coding RNA, meaning it is a stretch of DNA that produces an RNA molecule but does not code for a protein. Its specific biological role is not described in the current research for this variant.
What is highly sensitive cardiac troponin T and why does it matter?
Cardiac troponin T is a protein that helps regulate heart muscle contraction. When heart muscle cells are damaged, troponin T is released into the bloodstream. The highly sensitive version of the assay (hs-cTnT) can detect levels roughly 10 times lower than conventional tests, making it useful for identifying subtle heart muscle changes in people without obvious symptoms.
Is rs10091374 associated with heart disease risk?
Variants at the chromosome 8q13 locus identified in the hs-cTnT GWAS, including rs10091374, were not found to be associated with coronary heart disease in a companion case-control analysis in the same study. The genetic link to the biomarker level did not translate to a detected association with disease status.
In which tissues does rs10091374 affect LINC03020 expression?
GTEx v11 data from 953 donors show the alternate allele is associated with reduced LINC03020 expression in eight tissues: visceral adipose tissue, thyroid, pituitary, liver, esophagus muscularis, aorta, brain cortex, and cervical spinal cord. All effects point consistently toward lower expression with the alternate allele.
What does the NCOA2 gene do?
NCOA2, or nuclear receptor coactivator 2, is a protein that assists other regulatory proteins in controlling gene activity. The GWAS study notes that over-expression of NCOA2 can be detected in myoblasts (muscle precursor cells), though the mechanism linking NCOA2 variation to cardiac troponin T levels has not been established in the available sources.