ArticleHuman molecular genetics2017
Whole-genome sequencing study of serum peptide levels: the Atherosclerosis Risk in Communities study.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis 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.
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Who cites it
23 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
- Sodium-glucose cotransporter 2 inhibitors and constipation: a two-sample mendelian randomization study.Frontiers in pharmacology · 2026Article
- HUBMet: an integrative database and analytical platform for human blood metabolites and metabolite-protein associations.Genome biology · 2025Article
- Application of Mendelian randomization to explore metabolic pathways in colorectal cancer.Annals of medicine and surgery (2012) · 2025Article
- Vascular medicine in the 21World journal of clinical cases · 2024Review
- Identification of blood metabolites associated with risk of Alzheimer's disease by integrating genomics and metabolomics data.Molecular psychiatry · 2024Article
- Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.Nature communications · 2023Article
- Article
- Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes.Genome medicine · 2022Article
- Advances in integrative African genomics.Trends in genetics : TIG · 2022Review
- Dynamic patterns of postprandial metabolic responses to three dietary challenges.Frontiers in nutrition · 2022Article
- Advances and Utility of the Human Plasma Proteome.Journal of proteome research · 2021Review
- Sequencing-based genome-wide association studies reporting standards.Cell genomics · 2021Article
- The Propagation of Racial Disparities in Cardiovascular Genomics Research.Circulation. Genomic and precision medicine · 2021Review
- Exome sequence association study of levels and longitudinal change of cardiovascular risk factor phenotypes in European Americans and African Americans from the Atherosclerosis Risk in Communities Study.Genetic epidemiology · 2021Article
- Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.American journal of human genetics · 2021Article
- Genetics meets proteomics: perspectives for large population-based studies.Nature reviews. Genetics · 2021Review
- A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos.American journal of human genetics · 2020Article
- The promise and reality of therapeutic discovery from large cohorts.The Journal of clinical investigation · 2020Review
- Profile of genetic variations in severely calcified carotid plaques by whole-exome sequencing.Surgical neurology international · 2020Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Oligopeptides are important markers of protein metabolism, as they are cleaved from larger polypeptides and proteins. Genetic association studies may help elucidate their origin and function. In 1,552 European Americans and 1,872 African Americans of the Atherosclerosis Risk in Communities study, we performed whole-genome and whole-exome sequencing and measured serum levels of 25 peptides. Common variants (minor allele frequency > 5%) were analysed individually. We grouped low-frequency variants (minor allele frequency ≤ 5%) by a genome-wide sliding window using region-based aggregate tests. Furthermore, low-frequency regulatory variants were grouped by gene, as were functional coding variants. All analyses were performed separately in each ancestry group and then meta-analysed. We identified 22 common variant associations with peptide levels (P-value < 4.2 × 10-10), including 16 novel gene-peptide pairs. Notably, variants in kinin-kallikrein genes KNG1, F12, KLKB1, and ACE were associated with several different peptides. Variants in KLKB1 and ACE were associated with a fragment of complement component 3f. Both common variants and low-frequency coding variants in CPN1 were associated with a fibrinogen cleavage peptide. Four sliding windows were significantly associated with peptide levels (P-value < 4.2 × 10-10). Our results highlight the importance of the kinin-kallikrein system in the regulation of serum peptide levels, strengthen the evidence for a broad link between the kinin-kallikrein and complement systems, and suggest a role of CPN1 in the conversion of fibrinogen to fibrin.
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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.