rs12193973 (TARID/TCF21): Cardiovascular Locus
Key takeaways
- rs12193973 lies in the LINC01312/TARID locus, a region studied in large-scale cardiovascular genome-wide association research.
- The alternate allele increases TCF21 expression (a transcription factor involved in coronary artery cell biology) across six tissue types.
- TARID, the long non-coding RNA at this locus, shows increased expression specifically in coronary artery and lung tissue in carriers of the alternate allele.
- These expression effects are mechanism-level observations from GTEx v11 and do not establish direct causal links to cardiovascular disease outcomes.
Key takeaways
- rs12193973 lies in the LINC01312/TARID locus, a region studied in large-scale cardiovascular genome-wide association research.
- The alternate allele increases TCF21 expression (a transcription factor involved in coronary artery cell biology) across six tissue types.
- TARID, the long non-coding RNA at this locus, shows increased expression specifically in coronary artery and lung tissue in carriers of the alternate allele.
- These expression effects are mechanism-level observations from GTEx v11 and do not establish direct causal links to cardiovascular disease outcomes.
What the research says A multi-trait analysis of GWAS (MTAG) spanning 58 cardiac-related traits and diseases leveraged genetic correlations among atrial fibrillation (AF), coronary artery disease (CAD), and heart failure (HF) to improve genomic locus discovery, identifying 19 novel AF loci, 131 novel CAD loci, and 141 novel HF loci; polygenic scores derived from MTAG improved CAD prediction and discrimination in females versus conventional GWAS scores (ΔR² 1.735%, 95% CI 0.609-2.856; net reclassification index 0.208, 95% CI 0.139-0.277) in a validation cohort of 15,177 Canadian individuals. Functional data from GTEx v11 (953 donors) show the alternate allele at rs12193973 is an eQTL - a variant that influences nearby gene expression - for both TCF21 and TARID across multiple tissues, with the strongest TCF21 signal in cultured fibroblasts (p=7.0×10^-²³) and the strongest TARID signal in coronary artery tissue (p=7.3×10^-9) GTEx Portal.
Reported associations
- Novel cardiovascular loci (GWAS/MTAG): rs12193973 falls within the LINC01312/TARID locus, a region examined in a multi-trait cardiovascular GWAS/MTAG study that identified 131 novel CAD loci, 19 novel AF loci, and 141 novel HF loci across 58 cardiac traits; specific per-variant statistics for rs12193973 were not available in the provided materials.
- TCF21 expression (eQTL): The alternate allele increases TCF21 expression in cultured fibroblasts, esophagus muscularis, adrenal gland, tibial nerve, skeletal muscle, and subcutaneous adipose tissue GTEx Portal.
- TARID expression (eQTL): The alternate allele increases TARID expression in coronary artery and lung tissue GTEx Portal.
Evidence quality The cardiovascular GWAS/MTAG study is large-scale, integrating data across 58 cardiac traits with polygenic score validation in 15,177 Canadian individuals; however, the provided materials do not include per-variant statistics (p-value, odds ratio, or effect size) for rs12193973 specifically, which limits precision of the association claim for this locus. The GTEx v11 eQTL associations are well-powered (n=953 donors, FDR<0.05 threshold) and statistically robust: TCF21 signals range from p=7.0×10^-²³ in fibroblasts to p=1.2×10^-¹³ in skeletal muscle, while TARID signals reach p=7.3×10^-9 in coronary artery and p=2.4×10^-¹³ in lung GTEx Portal. No conflicting findings were present across the provided materials. eQTL effects are mechanistic observations describing how this variant influences gene expression levels, not whether it causes or prevents disease.
Tissue-specific expression effects
- TCF21: Increased expression in cultured fibroblasts, esophagus muscularis, adrenal gland, tibial nerve, skeletal muscle, and subcutaneous adipose tissue for carriers of the alternate allele GTEx Portal.
- TARID: Increased expression in coronary artery and lung tissue for carriers of the alternate allele GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is TARID and what does it do?
TARID (TCF21 antisense RNA inducing demethylation) is a long non-coding RNA, meaning it is transcribed from DNA but does not encode a protein. It is thought to regulate expression of the nearby TCF21 gene through mechanisms involving DNA methylation.
What is TCF21 and why is it relevant to the heart?
TCF21 is a transcription factor, a protein that controls which other genes are switched on or off. It plays roles in coronary artery smooth muscle cell development and has been implicated in coronary artery disease in multiple genomic studies.
Is rs12193973 linked to coronary artery disease?
rs12193973 falls within a locus studied in a large cardiovascular GWAS analysis that identified 131 novel coronary artery disease loci. The alternate allele also increases TARID expression specifically in coronary artery tissue, suggesting a potential functional role, though specific per-variant disease association statistics were not available in the provided literature.
What does it mean that rs12193973 is an eQTL?
An eQTL (expression quantitative trait locus) is a genetic variant that influences how much a nearby gene is expressed. For rs12193973, carriers of the alternate allele show higher TCF21 and TARID expression in multiple tissues, based on GTEx v11 data from 953 donors.
What is LINC01312?
LINC01312 is a long intergenic non-coding RNA, a class of RNA transcribed from DNA that does not produce protein. It is another name for TARID, the non-coding RNA at this locus that is thought to regulate nearby TCF21 gene expression.