ArticleBMC medicine2023
Genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and health outcomes: a drug-target Mendelian randomization study and a phenome-wide association study.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease.Nature cardiovascular research · 2026Article
- DNA methylation informs adult cardiovascular risk and prevention for low birthweight individuals.Journal of global health · 2026Article
- In vivo base editing of Asgr1 reduces blood lipids in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- ASGR1 Deficiency Promotes Liver Fibrosis by Enhancing Pro-Inflammatory Arachidonic Acid Metabolism and ALP Secretion.Immunity, inflammation and disease · 2026Article
- Increased Asialoglycoprotein Receptor 1 Level in Granulosa Cell as a Potential Biomarker for Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Serum Soluble Asialoglycoprotein Receptor 1: A Potential Predictor Marker Linked to Type 2 Diabetes Mellitus, Demonstrating Positive Correlation With High Sensitive C-Reactive Protein.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Unravelling the prognostic and operative role of intratumoural microbiota in non-small cell lung cancer: Insights from 16S rRNA and RNA sequencing.Clinical and translational medicine · 2025Article
- Asialoglycoprotein receptor 1: a multifaceted receptor in the liver and cardiovascular system.Frontiers in medicine · 2025Review
- Brain structures as potential mediators of the causal effect of COVID 19 on migraine risk.Scientific reports · 2024Article
- A translational framework of genoproteomic studies for cardiovascular drug discovery.NPJ cardiovascular health · 2024Article
- The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers.Lipids in health and disease · 2024Article
- Multi-omics Mendelian randomization integrating GWAS, eQTL, and mQTL data identified genes associated with breast cancer.American journal of cancer research · 2024Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAsialoglycoprotein receptor 1 (ASGR1) is emerging as a potential drug target to reduce low-density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD) risk. Here, we investigated genetically mimicked ASGR1 inhibitors on all-cause mortality and any possible adverse effects.
methodsWe conducted a drug-target Mendelian randomization study to assess genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and 25 a priori outcomes relevant to lipid traits, CAD, and possible adverse effects, i.e. liver function, cholelithiasis, adiposity and type 2 diabetes. We also performed a phenome-wide association study of 1951 health-related phenotypes to identify any novel effects. Associations found were compared with those for currently used lipid modifiers, assessed using colocalization, and replicated where possible.
resultsGenetically mimicked ASGR1 inhibitors were associated with a longer lifespan (3.31 years per standard deviation reduction in LDL-cholesterol, 95% confidence interval 1.01 to 5.62). Genetically mimicked ASGR1 inhibitors were inversely associated with apolipoprotein B (apoB), triglycerides (TG) and CAD risk. Genetically mimicked ASGR1 inhibitors were positively associated with alkaline phosphatase, gamma glutamyltransferase, erythrocyte traits, insulin-like growth factor 1 (IGF-1) and C-reactive protein (CRP), but were inversely associated with albumin and calcium. Genetically mimicked ASGR1 inhibitors were not associated with cholelithiasis, adiposity or type 2 diabetes. Associations with apoB and TG were stronger for ASGR1 inhibitors compared with currently used lipid modifiers, and most non-lipid effects were specific to ASGR1 inhibitors. The probabilities for colocalization were > 0.80 for most of these associations, but were 0.42 for lifespan and 0.30 for CAD. These associations were replicated using alternative genetic instruments and other publicly available genetic summary statistics.
conclusionsGenetically mimicked ASGR1 inhibitors reduced all-cause mortality. Beyond lipid-lowering, genetically mimicked ASGR1 inhibitors increased liver enzymes, erythrocyte traits, IGF-1 and CRP, but decreased albumin and calcium.
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