ArticleDiabetologia2013
Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 9 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 9 syntheses or guidelines pooled it.
- Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.Genome biology · 2022Pooled it
- Pooled it
- The influence of rare variants in circulating metabolic biomarkers.PLoS genetics · 2020Pooled it
- Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels.Journal of medical genetics · 2016Pooled it
- Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.Nature communications · 2016Pooled it
- Pleiotropic genes for metabolic syndrome and inflammation.Molecular genetics and metabolism · 2014Pooled it
- Meta-analysis of gene-level tests for rare variant association.Nature genetics · 2014Pooled it
- Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.PLoS genetics · 2013Pooled it
- Genomic study of maternal lipid traits in early pregnancy concurs with four known adult lipid loci.Journal of clinical lipidologyPooled it
- Functional ADAM12 variants modulate proteolytic activity and influence metabolic traits.Scientific reports · 2026Article
- A clinical and genotype-phenotype analysis of MACF1 variants.American journal of human genetics · 2025Article
- Article
- ZebrafishFrontiers in cell and developmental biology · 2024Article
- Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study.American journal of human genetics · 2023Article
- A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes.Nature metabolism · 2023Article
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications.Frontiers in physiology · 2023Review
- Article
- The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism.Journal of the Endocrine Society · 2022Article
- Diabetes: discovery of insulin, genetic, epigenetic and viral infection mediated regulation.The Nucleus : an international journal of cytology and allied topics · 2022Review
22 more citing papers are in PubMed but not listed here.
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108 authors.
Funding
Abstract
aims/hypothesisHuman complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes.
methodsThe study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans.
resultsExome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). CONCLUSIONS/
interpretationWe applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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