Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis
Qiao, J.; Wang, Q.; Zhao, Y.; Chang, M.; Cai, L.; Liu, F.; Yao, K.; Zheng, L.; Tan, N.; He, P.; Jegga, A. G.; Pauklin, S.; Jiang, L.; Yang, Y.; Feng, Y.
Show abstract
Telomere shortening, a marker of cellular aging and genomic instability, has been epidemiologically linked to an increased risk of various cardiovascular diseases (CVDs). However, shared genetic determinants involved in these associations remain unclear. We composed an atlas of the shared genetic associations between leukocyte telomere length (LTL) and six major CVDs by investigating shared genetic elements, encompassing SNPs, genes, biological pathways, and protein targets with pleiotropic implications. Extensive genetic overlaps beyond genetic correlations were observed, but no causal relationships were established. We identified 248 independent pleiotropic genomic risk loci, implicating 50 unique genes in two or more trait pairs, especially the SH2B3 gene, which was further validated by a proteome-wide Mendelian Randomization study. Functional analysis demonstrated a link to both DNA biosynthetic processes and telomere maintenance mechanisms. These findings suggest a genetic link between LTL and CVDs, highlighting a shared genetic basis crucial for developing future interventions and therapeutic targets.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistanis and Bangladeshis 96%
- Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories 96%
- Genome-wide association analysis and Mendelian randomization proteomics identify novel protein biomarkers and drug targets for primary prevention of heart failure 96%
Similar papers in this journal
- Integrative proteomic analyses across common cardiac diseases yield new mechanistic insights and enhanced prediction 96%
- Genetic and environmental determinants of diastolic heart function 95%
- Single cell compendium of muscle microenvironment in peripheral artery disease reveals altered endothelial diversity and LYVE1+ macrophage activation 93%
Similar papers in this journal
- A Statistical Framework to Identify Cell Types Whose Genetically Regulated Proportions are Associated with Complex Diseases 94%
- Novel Insights into Post-Myocardial Infarction Cardiac Remodeling through Algorithmic Detection of Cell-Type Composition Shifts 94%
- Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context 94%
Similar papers in this journal
- A loss-of-function CCR2 variant is associated with lower cardiovascular risk 96%
- Novel protein-altering variants associated with serum apolipoprotein and lipid levels 94%
- The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.