ArticlePLoS genetics2011
Discovery of sexual dimorphisms in metabolic and genetic biomarkers.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 7 of them syntheses that pooled it.
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Who cites it
228 citing papers in PubMed, 7 syntheses or guidelines pooled it, 400 citations in OpenAlex.
- A large-scale genome-wide association meta-analysis for nevus count provides direct insights into the genetics of melanoma.Nature communications · 2026Pooled it
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- Stress and circulating cell-free mitochondrial DNA: A systematic review of human studies, physiological considerations, and technical recommendations.Mitochondrion · 2021Pooled it
- Pooled it
- Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease.Journal of the American Heart Association · 2019Pooled it
- Assessing the causal association of glycine with risk of cardio-metabolic diseases.Nature communications · 2019Pooled it
- Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels.Nature communications · 2015Pooled it
- Plasma lipidomic and metabolomic profiles in high-grade glioma patients before and after 72-h presurgery water-only fasting.Molecular oncology · 2025Trial
- Age and sex are associated with the plasma lipidome: findings from the GOLDN study.Lipids in health and disease · 2021Trial
- Metabolic Predictors of Incident Coronary Heart Disease in Women.Circulation · 2018Trial
- Metabolomics and Machine Learning Uncover 5'-Methylthioadenosine as a Metabolic Indicator of Mixed-Pattern Drug-Induced Liver Injury.Metabolites · 2026Article
- Leisure-time physical activity and metabolomic trajectories over the transition from late midlife to old age.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- An LC-MS untargeted metabolomic comparison between three blood microsampling devices, whole blood, and plasma.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Sex-Specific Plasma Metabolomic Signatures in COPD Reveal Creatine, Purine/Urate, and Bile-Acid Axes.Metabolites · 2026Article
- Metabolomics Data Analysis with TIGER.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Dermatological implications of alignment-based de-hosting and bioinformatics pipelines on shotgun microbiome analysis.Journal of translational medicine · 2025Article
- Sex Modifies Metabolic Pathways Associated with Lipids in Untargeted Metabolomics: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2005-2006.Metabolites · 2025Article
- Genetic architecture and analysis practices of circulating metabolites in the NHLBI Trans-Omics for Precision Medicine Program.American journal of human genetics · 2025Article
- Towards non-invasive diagnosis of glioblastoma: identifying metabolic biomarkers in liquid biopsies using a ROC-based approach.Discover oncology · 2025Article
- Mitochondria-centred metabolomic map of inclusion body myositis: sex-specific alterations in central carbon metabolism.Annals of the rheumatic diseases · 2025Article
168 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8×10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8×10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation.
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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.