ArticlePLoS genetics2020
Linking protein to phenotype with Mendelian Randomization detects 38 proteins with causal roles in human diseases and traits.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 3 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- The genetic landscape of neuro-related proteins in human plasma.Nature human behaviour · 2024Pooled it
- Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes.Genome medicine · 2022Pooled it
- Gene-based whole genome sequencing meta-analysis of 250 circulating proteins in three isolated European populations.Molecular metabolism · 2022Pooled it
- Review
- Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026Review
- Efficient candidate drug target discovery through proteogenomics in a Scottish cohort.Communications biology · 2025Article
- Plasma proteome variation and its genetic determinants in children and adolescents.Nature genetics · 2025Article
- The causal relationship between circulating inflammatory proteins and heart failure: A two-sample Mendelian randomization study.Medicine · 2025Article
- Prediction of causal genes at GWAS loci with pleiotropic gene regulatory effects using sets of correlated instrumental variables.PLoS genetics · 2024Article
- Article
- Article
- Genetic determinants of plasma protein levels in the Estonian population.Scientific reports · 2024Article
- Investigating potential novel therapeutic targets and biomarkers for ankylosing spondylitis using plasma protein screening.Frontiers in immunology · 2024Article
- Article
- Genetic mechanisms of 184 neuro-related proteins in human plasma.medRxiv : the preprint server for health sciences · 2023Article
- A Targeted Proteomics Approach for Screening Serum Biomarkers Observed in the Early Stage of Type I Endometrial Cancer.Biomedicines · 2022Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies.Nature genetics · 2022Article
- Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19.PLoS genetics · 2022Article
- Inflammation proteomics datasets in the ALSPAC cohort.Wellcome open research · 2022Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances from GeneAtlas (UK Biobank), 77 showed little evidence of pleiotropy (HEIDI), and 92 evidence of colocalization (eCAVIAR). Results were wide ranging: including, for example, new evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia, and a new finding that intestinal fatty acid binding protein (FABP2) abundance contributes to the pathogenesis of cardiovascular disease. We also demonstrated confirmatory evidence for the causal role of four further proteins (FGF5, IL6R, LPL, LTA) in cardiovascular disease risk.
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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.