ArticleEBioMedicine2019
Evaluation of GDF15 as a therapeutic target of cardiometabolic diseases in human: A Mendelian randomization study.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 of them syntheses that pooled it.
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Who cites it
32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Association between growth differentiation factor 15 levels and gestational diabetes mellitus: A combined analysis.Frontiers in endocrinology · 2023Pooled it
- Pooled it
- The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study.BMC cardiovascular disorders · 2020Pooled it
- Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study.PLoS medicine · 2020Trial
- Trial
- Associations of Growth Differentiation Factor 15 in Chronic Kidney Disease.Kidney international reports · 2026Article
- Absence of GDF15 Aggravates Pressure Overload-Induced Cardiac Remodelling in Mice Hallmarked by Perivascular Fibrosis and Signs of Endothelial-to-Mesenchymal Transition.International journal of molecular sciences · 2026Article
- Sex-specific association between osteoporosis and cataracts: UK Biobank and Hong Kong Osteoporosis Study.Archives of osteoporosis · 2026Article
- Revisiting the role of GDF15 in atherosclerosis in mouse and human.Acta pharmacologica Sinica · 2025Article
- Metabolic Messenger: growth differentiation factor 15.Nature metabolism · 2025Review
- Causal relationship between serum metalloproteinase 12 levels and aortic dissection and aortic aneurysm: a bidirectional Mendelian randomization study.Journal of thoracic disease · 2025Article
- GDF-15 at admission predicts cardiovascular death, heart failure, and bleeding outcomes in patients with CAD.ESC heart failure · 2023Article
- Overview of growth differentiation factor 15 in metabolic syndrome.Journal of cellular and molecular medicine · 2023Review
- Effect of visceral adipose tissue mass on coronary artery disease and heart failure: A Mendelian randomization study.International journal of obesity (2005) · 2022Article
- Novel Biomarkers of Heart Failure in Pediatrics.Children (Basel, Switzerland) · 2022Review
- Metabolic syndrome and Growth Differentiation Factor 15 in older adults.GeroScience · 2022Article
- GDF15: a potential therapeutic target for type 1 diabetes.Expert opinion on therapeutic targets · 2022Review
- Deciphering the Causal Relationships Between Low Back Pain Complications, Metabolic Factors, and Comorbidities.Journal of pain research · 2022Article
- Synergistic insights into human health from aptamer- and antibody-based proteomic profiling.Nature communications · 2021Observational
- Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study.Human reproduction (Oxford, England) · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGrowth differentiation factor 15 (GDF15) is a key regulator of body weight in animals by regulating food intake. Its receptor, glial cell-derived neurotrophic factor receptor alpha-like (GFRAL), was identified recently. Pre-clinical studies showed that it is a promising therapeutic target for cardiometabolic diseases and anorexia/cachexia. Although many pharmaceutical companies are developing drugs targeting GFRAL, whether the findings from animal studies can be extrapolated to man is unknown. Mendelian randomization (MR) is useful in investigating the relationship between risk factors and disease outcomes. We aimed to use a two-sample MR approach to evaluate the clinical usefulness of targeting GDF15 for cardiometabolic diseases.
methodsGenetic instruments and summary statistics for MR analyses were obtained from a large genome-wide association study (GWAS) of GDF15 and cardiometabolic outcomes (n = 27,394 to 644,875), including body mass index, waist-hip ratio, waist circumference, whole-body lean mass, fat percentage, Type 2 Diabetes, fasting glucose, glycated haemoglobin, fasting insulin, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglycerides, coronary artery disease, and estimated BMD (eBMD). Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of GDF-15 with different outcomes; weighted median and MR-egger were used for sensitivity analyses.
findingsThere was null association between GDF15 levels and anthropometric outcomes. One SD increase in genetically-determined GDF15 was significantly associated with reduced HDL-C (beta: -0.048SD; SE: 0.014; P = .001) but the result was not significant in sensitivity analyses. A consistent significant causal association was observed between GDF15 and eBMD in IVW (beta: 0.026 SD; SE: 0.005; P < .001) and subsequent sensitivity analyses.
interpretationThis study sheds lights on the potential of drugs targeting the GDF15/GFRAL axis. It suggested that the effect of targeting GDF15/GFRAL axis for weight control in human may be different from the effects observed in animal studies. GDF15 treatment may improve BMD in humans. FUND: No specific funding was received for this study.
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