Full
Outline
To identify causal genes associated with frailty, a significant global health issue whose genetic mechanisms remain poorly understood, by integrating multi-tissue gene expression data.
This study integrated expression quantitative trait loci（eQTL）data from 49 human tissues and employed summary data-based Mendelian randomization（SMR）to analyze causal associations between gene expression and frailty. Genetic colocalization of signals was used to validate significant genes, followed by sensitivity analysis using two-sample Mendelian randomization, with MR-Egger regression and Cochran’s Q test to control for pleiotropy and heterogeneity. Gene Ontology（GO）enrichment analysis was performed for genes identified through SMR, colocalization, and sensitivity analyses.
Twenty causal genes（80 significant associations）linked to frailty were identified across 27 tissues. The top five genes showing multi-tissue causal associations included LRPPRC, RBM6, TTC12, RNF123, and CPS1. The final 20 causal genes were primarily enriched in mitochondrial function regulation, nuclear-mitochondrial signaling, and redox metabolic processes.
The causal genes identified in this study may influence the occurrence and development of frailty through mitochondrial function and nuclear signaling pathways.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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