GLP-1R expression protects against 58 diseases but raises risk for 34 diseases and neonatal health
Campbell, R. H.; Mills, M. C.
Show abstract
Cardiometabolic gene-target drugs such as Glucagon-Like Peptide 1 Receptor agonists are used extensively, yet risks and repurposing have not been systematically evaluated across a comprehensive set of diseases. We use Phenome-wide Mendelian Randomization to test GLP1R gene expression and Cholesteryl Ester Transfer Protein (CETP) concentration, two promising cardiometabolic drug targets, on risk of 396 diseases based on sex-specific, ancestry-specific, genome-wide association studies in UK Biobank. We identify 92 causal effects (66 novel) of genetically proxied GLP1R expression on disease, with 58 protective and 34 risk effects. Risks of GLP1R expression on neonatal health raise concern for women who may become pregnant. GLP1R expression substantially increases risk of Vitamin D deficiency. Although GLP1R is hypothesized as anti-ageing, we find it increases risk of 22 age-related diseases. Conversely, we find CETP inhibition is narrowly cardioprotective. Results show benefits, risks and repurposing opportunities for GLP1R-targetted and CETP-targeted drugs.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases 96%
- A combined polygenic score of 21,293 rare and 22 common variants significantly improves diabetes diagnosis based on hemoglobin A1C levels 96%
- Genetic effects on the timing of parturition and links to fetal birth weight 96%
Similar papers in this journal
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities 96%
- Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension 95%
- Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19 95%
Similar papers in this journal
- Human genetic analyses of organelles highlight the nucleus in age-related trait heritability 95%
- Germline burden of rare damaging variants negatively affects human healthspan and lifespan 95%
- Chromatin accessibility variation provides insights into missing regulation underlying immune-mediated diseases 95%
Similar papers in this journal
- Evidence for the role of selection for reproductively advantageous alleles in human aging 96%
- Bidirectional Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of intermediate potential 94%
- Desert Dingo (Canis lupus dingo) genome provides insights into their role in the Australian ecosystem. 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.