ArticleBMC medical genomics2024
Proteome-wide mendelian randomization investigates potential associations in heart failure and its etiology: emphasis on PCSK9.
Article in BMC medical genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies.Cell communication and signaling : CCS · 2025Article
- Causality of blood metabolites and narcolepsy type 1: A Mendelian randomization study.Medicine · 2025Article
- Mendelian randomization of plasma lipidome, inflammatory proteome and heart failure.ESC heart failure · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHeart failure (HF) is a prevalent clinical syndrome with diverse etiologies. It is crucial to identify novel therapeutic targets based on underlying causes. Here, we aimed to use proteome-wide Mendelian randomization (MR) analyses to identify the associations between genetically predicted elevated levels of circulating proteins and distinct HF outcomes, along with specific HF etiologies.
methodsProtein quantitative trait loci (pQTL) data for circulating proteins were sourced from the Atherosclerosis Risk in Communities (ARIC) study, encompassing 7,213 individuals and profiling 4,657 circulating proteins. Genetic associations for outcomes were obtained from the HERMES Consortium and the FinnGen Consortium. Colocalization analysis was employed to assess the impact of linkage disequilibrium on discovered relationships. For replication, two-sample MR was conducted utilizing independent pQTL data from the deCODE study. Multivariable MR (MVMR) and two-step MR were further conducted to investigate potential mediators.
resultsTwo proteins (PCSK9 and AIDA) exhibited associations with HF in patients with coronary heart disease (CHD), and four proteins (PCSK9, SWAP70, NCF1, and RELT) were related with HF in patients receiving antihypertensive medication. Among these associations, strong evidence from subsequent analyses supported the positive relationship between genetically predicted PCSK9 levels and the risk of HF in the context of CHD. Notably, MVMR analysis revealed that CHD and LDL-C did not exert a complete mediating effect in this relationship. Moreover, two-step MR results yielded valuable insights into the potential mediating proportions of CHD or LDL-C in this relationship.
conclusionsOur findings provide robust evidence supporting the association between PCSK9 and concomitant HF and CHD. This association is partly elucidated by the influence of CHD or LDL-C, underscoring the imperative for additional validation of this connection and a thorough exploration of the mechanisms through which PCSK9 directly impacts ischemic HF.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.