ArticleBMC genomics2024
Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.
Article in BMC genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Integration of GWAS, QTLs and keratinocyte functional assays reveals molecular mechanisms of atopic dermatitis.Nature communications · 2025Pooled it
- Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes.HGG advances · 2024Pooled it
- Trial
- Neuronal Cell-Specific sc-eQTL and Integrative eQTL-pQTL Mendelian Randomization Prioritize CKAP2 as a Candidate Gene for Major Depressive Disorder.Journal of molecular neuroscience : MN · 2026Observational
- Integration of genetic evidence to identify approved drug targets.Genome medicine · 2026Article
- Multi-Omic Insight Into the Molecular Networks of Mitochondrial Dysfunction in the Pathogenesis of Schizophrenia.Schizophrenia bulletin · 2026Article
- Phospholipase D2: A biomarker for stratifying disease severity in acute pancreatitis?World journal of gastroenterology · 2025Article
- Efficient count-based models improve power and robustness for large-scale single-cell eQTL mapping.medRxiv : the preprint server for health sciences · 2025Article
- Pancreatic cancer subtyping - the keystone of precision treatment.Frontiers in immunology · 2025Review
- SciLinker: a large-scale text mining framework for mapping associations among biological entities.Frontiers in artificial intelligence · 2025Article
- A multi-stage genomic approach to uncover druggable gene targets and neural pathways in postpartum depression.Archives of medical science : AMS · 2025Article
- Multi-ancestry Genome-Wide Association Meta-Analysis Identifies Novel Loci in Atopic Dermatitis.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
13 authors.
Funding
Abstract
backgroundTherapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes. Careful interpretation remains warranted because eQTL can affect the expression of multiple genes within the same locus.
methodsWe used a combination of genomic features that include variant annotation, activity-by-contact maps, MR, and colocalization with molQTL to prioritize causal genes across 4,611 disease GWAS and meta-analyses from biobank studies, namely FinnGen, Estonian Biobank and UK Biobank.
resultsGenes identified using this approach are enriched for gold standard causal genes and capture known biological links between disease genetics and biology. In addition, we find that eQTL colocalizing with GWAS are statistically enriched for corresponding disease-relevant tissues. We show that predicted directionality from MR is generally consistent with matched drug mechanism of actions (> 85% for approved drugs). Compared to the nearest gene mapping method, genes supported by multi-omics evidences displayed higher enrichment in approved therapeutic targets (risk ratio 1.75 vs. 2.58 for genes with the highest level of support). Finally, using this approach, we detected anassociation between the IL6 receptor signal transduction gene IL6ST and polymyalgia rheumatica, an indication for which sarilumab, a monoclonal antibody against IL-6, has been recently approved.
conclusionsCombining variant annotation, activity-by-contact maps, and molQTL increases performance to identify causal genes, while informing on directionality which can be translated to successful target identification and drug development.
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