ArticleNature communications2021
Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Use of Mendelian Randomization to Unveil Metabolic Markers inJournal of Korean medical science · 2026Pooled it
- Personalized whole-body modeling links gut microbiota to metabolic perturbations in Alzheimer's disease.Gut microbes · 2026Article
- Genome-wide association studies of missing metabolite measures from two population-based studies.Genome biology · 2026Article
- Article
- Ancestry-specific genetics of amino acids and microbiota-related metabolites reveal causal effects on cardiometabolic disease in Chinese populations.Cardiovascular diabetology · 2026Article
- Integration of metabolomic and genetic data reveals novel variants underpinning the human metabolome: the Coronary Artery Risk Development in Young Adults (CARDIA) study.medRxiv : the preprint server for health sciences · 2026Article
- Widely targeted metabolomics and machine learning identify succinate as a key metabolite in sepsis-associated encephalopathy.iScience · 2026Article
- Application of Mendelian randomization to explore metabolic pathways in colorectal cancer.Annals of medicine and surgery (2012) · 2025Article
- Metabolic modeling links gut microbiota to metabolic markers of Parkinson's disease.Gut microbes · 2025Article
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
- Genetic determinants of urine and plasma metabolite levels.Nature reviews. Nephrology · 2025Article
- Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.Nature genetics · 2025Article
- In silico metabolic modelling links microbiome-derived metabolites to risk factors of Alzheimer's disease.Gut microbes reports · 2025Article
- Genetic architecture of cerebrospinal fluid and brain metabolite levels and the genetic colocalization of metabolites with human traits.Nature genetics · 2024Article
- A genome-wide association study of neonatal metabolites.Cell genomics · 2024Article
- Genome-scale metabolic models applied for human health and biopharmaceutical engineering.Quantitative biology (Beijing, China) · 2023Review
- Metabolomics and lipidomics strategies in modern drug discovery and development.Drug discovery today · 2023Review
- Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia.BMC medicine · 2023Article
- IDSL.CSA: Composite Spectra Analysis for Chemical Annotation of Untargeted Metabolomics Datasets.Analytical chemistry · 2023Article
- Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.Nature genetics · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolite levels in urine may provide insights into genetic mechanisms shaping their related pathways. We therefore investigate the cumulative contribution of rare, exonic genetic variants on urine levels of 1487 metabolites and 53,714 metabolite ratios among 4864 GCKD study participants. Here we report the detection of 128 significant associations involving 30 unique genes, 16 of which are known to underlie inborn errors of metabolism. The 30 genes are strongly enriched for shared expression in liver and kidney (odds ratio = 65, p-FDR = 3e-7), with hepatocytes and proximal tubule cells as driving cell types. Use of UK Biobank whole-exome sequencing data links genes to diseases connected to the identified metabolites. In silico constraint-based modeling of gene knockouts in a virtual whole-body, organ-resolved metabolic human correctly predicts the observed direction of metabolite changes, highlighting the potential of linking population genetics to modeling. Our study implicates candidate variants and genes for inborn errors of metabolism.
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