ArticlePLoS genetics2012
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 6 of them syntheses 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.
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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
103 citing papers in PubMed, 6 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- Use of Mendelian Randomization to Unveil Metabolic Markers inJournal of Korean medical science · 2026Pooled it
- Integration ofFrontiers in immunology · 2023Pooled it
- Multivariate analysis of genome-wide data to identify potential pleiotropic genes for five major psychiatric disorders using MetaCCA.Journal of affective disorders · 2019Pooled it
- metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis.Bioinformatics (Oxford, England) · 2016Pooled it
- Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways.BMC medical genomics · 2015Pooled it
- Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.PLoS genetics · 2014Pooled it
- Proteomic Analysis of Human Plasma during Intermittent Fasting.Journal of proteome research · 2019Trial
- Genome metabolome integrated network analysis to uncover connections between genetic variants and complex traits: an application to obesity.Journal of the Royal Society, Interface · 2014Trial
- Identification of genetic variants influencing the human plasma proteome.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Application of Mendelian randomization to explore metabolic pathways in colorectal cancer.Annals of medicine and surgery (2012) · 2025Article
- PPP1R3B Suppresses Atherosclerosis by Promoting the M2 Polarization of Macrophages Through Glycogen Metabolic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Alpha1-Antitrypsin in Lung Diseases: A Cross-Sectional Observational Study.International journal of molecular sciences · 2025Observational
- Branched-chain amino acids promote hepatic Cyp7a1 expression and bile acid synthesis via suppressing FGF21-ERK pathway.Acta pharmacologica Sinica · 2025Article
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- A flexible empirical Bayes approach to multivariate multiple regression, and its improved accuracy in predicting multi-tissue gene expression from genotypes.PLoS genetics · 2023Article
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- miR-330-3p alleviates the progression of atherosclerosis by downregulating AQP9.Functional & integrative genomics · 2023Article
- Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants.Scientific data · 2023Article
- Pediatric Population with Down Syndrome: Obesity and the Risk of Cardiovascular Disease and Their Assessment Using Omics Techniques-Review.Biomedicines · 2022Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 13 institutions in 5 countries.
Funding
Abstract
Association testing of multiple correlated phenotypes offers better power than univariate analysis of single traits. We analyzed 6,600 individuals from two population-based cohorts with both genome-wide SNP data and serum metabolomic profiles. From the observed correlation structure of 130 metabolites measured by nuclear magnetic resonance, we identified 11 metabolic networks and performed a multivariate genome-wide association analysis. We identified 34 genomic loci at genome-wide significance, of which 7 are novel. In comparison to univariate tests, multivariate association analysis identified nearly twice as many significant associations in total. Multi-tissue gene expression studies identified variants in our top loci, SERPINA1 and AQP9, as eQTLs and showed that SERPINA1 and AQP9 expression in human blood was associated with metabolites from their corresponding metabolic networks. Finally, liver expression of AQP9 was associated with atherosclerotic lesion area in mice, and in human arterial tissue both SERPINA1 and AQP9 were shown to be upregulated (6.3-fold and 4.6-fold, respectively) in atherosclerotic plaques. Our study illustrates the power of multi-phenotype GWAS and highlights candidate genes for atherosclerosis.
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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 OpenQuestion graph.