ArticleHuman molecular genetics2018
Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05495074 (Design of a Genetic Score to Predict the Response to a Dietary Intervention in Adults With Metabolic Syndrome), which is not on this map. Cited by 24 papers, 4 of them syntheses that pooled it.
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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.
Design of a Genetic Score to Predict the Response to a Dietary Intervention in Adults With Metabolic Syndrome
Who cites it
24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Use of Mendelian Randomization to Unveil Metabolic Markers inJournal of Korean medical science · 2026Pooled it
- The influence of rare variants in circulating metabolic biomarkers.PLoS genetics · 2020Pooled 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
- Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE trial.Diabetologia · 2018Trial
- Application of Mendelian randomization to explore metabolic pathways in colorectal cancer.Annals of medicine and surgery (2012) · 2025Article
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
- Dissecting genetic regulation of metabolic coordination.Briefings in bioinformatics · 2025Article
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.Lipids in health and disease · 2024Article
- A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients.Critical care explorations · 2024Article
- Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease.Metabolites · 2023Article
- Article
- Extent to which array genotyping and imputation with large reference panels approximate deep whole-genome sequencing.American journal of human genetics · 2022Article
- Crosstalk between Host Genome and Metabolome among People with HIV in South Africa.Metabolites · 2022Article
- Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.Nature communications · 2022Article
- TheInternational journal of molecular sciences · 2022Article
- Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.BMC medicine · 2021Article
- Inborn errors of enzymes in glutamate metabolism.Journal of inherited metabolic disease · 2020Review
- Effect of non-normality and low count variants on cross-phenotype association tests in GWAS.European journal of human genetics : EJHG · 2020Article
Corrections and comments
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Authors and funding
32 authors at 12 institutions in 5 countries.
Funding
Abstract
Comprehensive metabolite profiling captures many highly heritable traits, including amino acid levels, which are potentially sensitive biomarkers for disease pathogenesis. To better understand the contribution of genetic variation to amino acid levels, we performed single variant and gene-based tests of association between nine serum amino acids (alanine, glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, tyrosine, and valine) and 16.6 million genotyped and imputed variants in 8545 non-diabetic Finnish men from the METabolic Syndrome In Men (METSIM) study with replication in Northern Finland Birth Cohort (NFBC1966). We identified five novel loci associated with amino acid levels (P = < 5×10-8): LOC157273/PPP1R3B with glycine (rs9987289, P = 2.3×10-26); ZFHX3 (chr16:73326579, minor allele frequency (MAF) = 0.42%, P = 3.6×10-9), LIPC (rs10468017, P = 1.5×10-8), and WWOX (rs9937914, P = 3.8×10-8) with alanine; and TRIB1 with tyrosine (rs28601761, P = 8×10-9). Gene-based tests identified two novel genes harboring missense variants of MAF <1% that show aggregate association with amino acid levels: PYCR1 with glycine (Pgene = 1.5×10-6) and BCAT2 with valine (Pgene = 7.4×10-7); neither gene was implicated by single variant association tests. These findings are among the first applications of gene-based tests to identify new loci for amino acid levels. In addition to the seven novel gene associations, we identified five independent signals at established amino acid loci, including two rare variant signals at GLDC (rs138640017, MAF=0.95%, Pconditional = 5.8×10-40) with glycine levels and HAL (rs141635447, MAF = 0.46%, Pconditional = 9.4×10-11) with histidine levels. Examination of all single variant association results in our data revealed a strong inverse relationship between effect size and MAF (Ptrend<0.001). These novel signals provide further insight into the molecular mechanisms of amino acid metabolism and potentially, their perturbations in disease.
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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.