Disentangling shared genetic etiologies for kidney function and cardiovascular diseases
Qiao, J.; Yao, K.; Yuan, Y.; Yang, X.; Zhou, L.; Long, Y.; Chen, M.; Xie, W.; Yang, Y.; Cao, Y.; Pauklin, S.; Xu, J.; Yang, Y.; Feng, Y.
Show abstract
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with chronic kidney disease (CKD) identified as a significant risk factor. CKD is primarily monitored through the estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation. Although epidemiological and clinical studies have consistently demonstrated strong associations between eGFR and CVDs, the genetic underpinnings of this relationship remain elusive. Recent genome-wide association studies (GWAS) have highlighted the polygenic nature of these conditions and identified several risk loci correlating with their cross-phenotypes. Nonetheless, the extent and pattern of their pleiotropic effects have yet to be fully elucidated. We analyzed the most comprehensive GWAS summary statistics, involving around 7.5 million individuals, to investigate the shared genetic architectures and the underlying mechanisms between eGFR and CVDs, focusing on single nucleotide polymorphisms (SNPs), genes, biological pathways, and proteins exhibiting pleiotropic effects. Our study identified 508 distinct genomic locations associated with pleiotropic effects across multiple traits, involving 379 unique genes, notably L3MBTL3 (6q23.1), MMP24 (20q11.22), and ABO (9q34.2). Additionally, pathways such as stem cell population maintenance and the glutathione metabolism pathway were pivotal in mediating the relationships between these traits. From the perspective of vertical pleiotropy, our findings suggest a causal relationship between eGFR and conditions such as atrial fibrillation and venous thromboembolism. These insights significantly enhance our understanding of the genetic links between eGFR and CVDs, potentially guiding the development of novel therapeutic strategies and improving the clinical management of these conditions.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Dissecting the Genetic Architecture of Intracranial Aneurysms 97%
- Transethnic meta-analysis of genome-wide association studies identifies three new loci and characterizes population-specific differences for coronary artery disease 95%
- Augmenting clinical risk prediction of cardiovascular disease through protein and epigenetic biomarkers 95%
Similar papers in this journal
- Genome-Wide Associations Of Aortic Distensibility Suggest Causal Relationships With Aortic Aneurysms And Brain White Matter Hyperintensities 96%
- Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistanis and Bangladeshis 95%
- Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure 95%
Similar papers in this journal
- Single-cell transcriptome-wide Mendelian randomization and colocalization analyses uncover cell-specific mechanisms in atherosclerotic cardiovascular disease 96%
- Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension 96%
- Genetic association studies using disease liabilities from deep neural networks 95%
Similar papers in this journal
- Epigenomic prediction of cardiovascular disease risk and interactions with traditional risk metrics 94%
- Leveraging genetic data to elucidate the relationship between Covid-19 and ischemic stroke 94%
- Blood pressure, cardiometabolic traits and cardiovascular events in women with uterine fibroids: a genetic correlation and Mendelian randomization study 94%
Similar papers in this journal
- Large-scale brainstem neuroimaging and genetic analyses provide new insights into the neuronal mechanisms of hypertension 94%
- An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential for early cardiovascular disease intervention 94%
- A year of COVID-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers 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.