Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank.

Fan Yi, Jing Yuan, Judith Somekh, Mor Peleg, Yi-Cheng Zhu, Zhilong Jia, Fei Wu, Zhengxing Huang

College of Computer Science and Technology, Zhejiang University, Hangzhou, China.College of Computer Science and Technology, Zhejiang University, Hangzhou, China. · pubmed

Paper

Abstract

Brain age gap (BAG), the deviation between estimated brain age and chronological age, is a promising marker of brain health. However, the genetic architecture and reliable targets for brain aging remains poorly understood. In this study, we estimate magnetic resonance imaging (MRI)-based brain age using deep learning models trained on the UK Biobank and validated with three external datasets. A genome-wide association study for BAG identified two unreported loci and seven previously reported loci. By integrating Mendelian Randomization (MR) and colocalization analysis on eQTL and pQTL data, we prioritized seven genetically supported druggable genes, including

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Research summary

The study identifies genetically supported druggable genes associated with brain aging and explores their potential for drug repurposing. This paper is relevant as it investigates genetic targets that could address the underlying mechanisms of brain aging, rather than merely treating symptoms of age-related diseases.

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