| Title: | Multi-layered genetic approaches to identify approved drug targets |
| Journal: | Cell Genomics |
| Published: | 15 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37492104/ |
| DOI: | https://doi.org/10.1016/j.xgen.2023.100341 |
| Citations: | 16 (15 in last 2 years) as of 8 Aug 2024 |
Publication 10526
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Abstract
Drugs targeting genes linked to disease via evidence from human genetics have increased odds of approval. Approaches to prioritize such genes include genome-wide association studies (GWASs), rare variant burden tests in exome sequencing studies (Exome), or integration of a GWAS with expression/protein quantitative trait loci (eQTL/pQTL-GWAS). Here, we compare gene-prioritization approaches on 30 clinically relevant traits and benchmark their ability to recover drug targets. Across traits, prioritized genes were enriched for drug targets with odds ratios (ORs) of 2.17, 2.04, 1.81, and 1.31 for the GWAS, eQTL-GWAS, Exome, and pQTL-GWAS methods, respectively. Adjusting for differences in testable genes and sample sizes, GWAS outperforms e/pQTL-GWAS, but not the Exome approach. Furthermore, performance increased through gene network diffusion, although the node degree, being the best predictor (OR = 8.7), revealed strong bias in literature-curated networks. In conclusion, we systematically assessed strategies to prioritize drug target genes, highlighting the promises and pitfalls of current approaches.</p>
4 Authors
- Marie C. Sadler
- Chiara Auwerx
- Patrick Deelen
- Zoltán Kutalik
1 Application
| Application ID | Title |
|---|---|
| 16389 | Exploring Diet/Lifestyle factors as causes and modifiers of genetic determinants of obesity and metabolic traits |
Enabling scientific discoveries that improve human health