ArticleHuman molecular genetics2023
Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Genetic and molecular signatures highlight diverse pathways linking obesity to type 2 diabetes.Nature communications · 2026Article
- Multi-trait GWAS reveals divergent local and polygenic architecture of cardiovascular traits across African and European ancestries in the UK Biobank.Communications biology · 2026Article
- Linking the plasma proteome to genetics in individuals from continental Africa provides insights into type 2 diabetes pathogenesis.Nature genetics · 2026Article
- Transcriptome remodelling and changes in growth and cardiometabolic phenotype result following Grb10a knockdown in the early life of the zebrafish.Cellular and molecular life sciences : CMLS · 2025Article
- Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health.npj metabolic health and disease · 2025Article
- A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank.Nature communications · 2024Article
- Multi-omics characterization of type 2 diabetes associated genetic variation.medRxiv : the preprint server for health sciences · 2024Article
- Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.JAMA cardiology · 2024Article
- Genetic Evidence for the Causal Link Between Coagulation Factors and the Risk of Ovarian Cancer: A Two-Sample Mendelian Randomization Study.International journal of women's health · 2024Article
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356; 22.5× WGS) and Pomak (n = 1537; 18.4× WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency < 1%). We additionally find 15 pQTL variants that are rare in non-Finnish European populations but have drifted up in the frequency in the discovery cohorts here. We identify proteins causally associated with cardiometabolic traits, including Mep1b for high-density lipoprotein (HDL) levels, and describe a knock-out (KO) Mep1b mouse model. Our findings furnish insights into the genetic architecture of the serum proteome, identify new protein-disease relationships and demonstrate the importance of isolated populations in pQTL analysis.
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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.