Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Nov. 19, 2024

Abstract Background Therapeutic 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 variants and phenotypic variation; however, identifying the genes driving associations identified remains challenging. Integration molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) colocalization analyses can help with identification causal genes. Careful interpretation warranted because eQTL affect multiple within same locus. Methods We used combination genomic features that include variant annotation, activity-by-contact maps, MR, molQTL prioritize across 4,611 disease meta-analyses biobank studies, namely FinnGen, Estonian Biobank UK Biobank. Results Genes this are enriched for gold standard capture known biological genetics biology. In addition, we find colocalizing statistically corresponding disease-relevant tissues. predicted directionality MR generally consistent matched drug mechanism actions (> 85% approved drugs). Compared nearest gene mapping method, multi-omics evidences displayed enrichment therapeutic (risk ratio 1.75 vs. 2.58 highest level support). Finally, approach, detected anassociation IL6 receptor signal transduction IL6ST polymyalgia rheumatica, an indication which sarilumab, monoclonal antibody against IL-6, has been recently approved. Conclusions Combining increases performance genes, while informing on be translated successful target development.

Language: Английский

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Spleen volume in relation to ulcerative colitis and Crohn’s disease: a Mendelian randomization study

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 24, 2025

Prior research has established the significance of spleen volume (SV) in pathogenesis and advancement ulcerative colitis (UC) Crohn's disease (CD). Nevertheless, these investigations are predominantly observational, thereby leaving their causal associations ambiguous. Moreover, breadth existing is constrained by various uncontrollable variables clinical settings. This study aims to deduce link between SV susceptibility UC CD through a genetic perspective. The objective this was investigate association inflammatory bowel (IBD) risk using Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) associated with were used as instrumental variables. Genetic for extracted from International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), FinnGen study, other publicly available genome-wide studies (GWAS). Methods such inverse variance weighted, Bayesian weighted (BWMR), contamination mixture (ConMix), along sensitivity analyses Steiger test study. A meta-analysis conducted synthesize results. found that genetically predicted an increased IIBDGC dataset (OR = 1. 223, 95% CI: 055–1. 417, P 0. 008), 169, 003–1. 363, 045), GWAS Sakaue S 188, 008–1. 399, 040), 115, 014–1. 227, 025). Similarly, 235, 026–1. 488, 026), 308, 667, 030), Zorina-Lichtenwalter K 316, 037–1. 670, 024), 272, 133–1. 428, < 001). According results, each standard unit increase SV, developing increases 11. 5%, 27. 2%. presents findings suggest positive onset IBD.

Language: Английский

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Positron Emission Tomography/Computed Tomography in Polymyalgia Rheumatica: When and for What—A Critical Review

Diagnostics, Journal Year: 2024, Volume and Issue: 14(14), P. 1539 - 1539

Published: July 17, 2024

Polymyalgia rheumatica (PMR) is an inflammatory disease common in people aged 50 years and older. This condition characterized by the presence of pain stiffness involving mainly shoulder pelvic girdle. Besides frequent association with giant cell arteritis (GCA), several conditions may mimic PMR or present features. Since diagnosis basically clinical, adequate this usually required. Positron emission tomography/computed tomography (PET-CT) has proved to be a useful tool for PMR. The use 18F-FDG-PET imaging appears promising as it provides detailed information on activity that not evident traditional methods. However, since PET-CT strictly necessary PMR, clinicians should consider situations which technique can used patients suspected

Language: Английский

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Traditional and Emerging Strategies for Managing Polymyalgia Rheumatica: Insights into New Treatments

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(21), P. 6492 - 6492

Published: Oct. 29, 2024

Polymyalgia Rheumatica (PMR) is an inflammatory condition that primarily affects individuals aged 50 and older, especially in Western countries. Although glucocorticoids are the cornerstone of PMR treatment, these drugs associated with side effects, making it advisable to use them for shortest duration possible. However, tapering or discontinuation often leads disease relapses. In this review, we focus on traditional management PMR, as well potential therapies may reduce glucocorticoid use. Special attention given efficacy biologic agents management.

Language: Английский

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