SynthesisPLoS genetics2020
The influence of rare variants in circulating metabolic biomarkers.
Synthesis in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- An atlas of genome-wide gene expression and metabolite associations and possible mediation effects towards body mass index.Journal of molecular medicine (Berlin, Germany) · 2023Pooled it
- Intragenic deletions from whole genome sequencing of 1054 suicide deaths.Research square · 2026Article
- Metabolic Adaptation in Acute Ischemic Events: The Critical Role of Acyl-Coenzyme A Synthetase Family in Myocardial Infarction and Ischemic Stroke.Journal of the American Heart Association · 2026Review
- Long-term isolation and archaic introgression shape functional genetic variation in Near Oceania.Science (New York, N.Y.) · 2026Article
- GWAS and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating fatty acids.HGG advances · 2025Article
- Genetic Risk Profiles for Atherosclerosis and Venous Thromboembolism in Azorean and Mainland Portuguese Populations: A Comparative Analysis.Current issues in molecular biology · 2025Article
- Merging metabolomics and genomics provides a catalog of genetic factors that influence molecular phenotypes in pigs linking relevant metabolic pathways.Genetics, selection, evolution : GSE · 2025Article
- The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes.Nature genetics · 2025Article
- Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.Nature genetics · 2025Article
- Genome-wide association studies and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating polyunsaturated, monounsaturated, and saturated fatty acids.medRxiv : the preprint server for health sciences · 2024Article
- Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.American journal of human genetics · 2022Article
- Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability.Nature communications · 2022Article
- Molecular Quantitative Trait Locus Mapping in Human Complex Diseases.Current protocols · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). Here we studied, association of rare variants and 226 serum lipoproteins, lipids and amino acids in 7,142 (discovery plus follow-up) healthy participants. We leveraged the information from multiple metabolite measurements on the same participants to improve discovery in rare variant association analyses for gene-based and gene-set tests by incorporating correlated metabolites as covariates in the validation stage. Gene-based analysis corrected for the effective number of tests performed, confirmed established associations at APOB, APOC3, PAH, HAL and PCSK (p<1.32x10-7) and identified novel gene-trait associations at a lower stringency threshold with ACSL1, MYCN, FBXO36 and B4GALNT3 (p<2.5x10-6). Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene-set analyses also corrected for effective number of tests, with IDL and LDL parameters, as well as circulating cholesterol (pMETASKAT<2.41x10-6). In conclusion, using an approach that leverages metabolite measurements obtained in the same participants, we identified novel loci and pathways involved in the regulation of these important metabolic biomarkers. As large-scale biobanks continue to amass sequencing and phenotypic information, analytical approaches such as ours will be useful to fully exploit the copious amounts of biological data generated in these efforts.
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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.