Xinyi Luo, Changjing Wu, Yang Xiong, Wei Wang, Qing Jiang, Zhihong Liu
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引用次数: 0
Abstract
Background: Benign prostatic hyperplasia (BPH) represents a prevalent age-related disorder with suboptimal pharmacological management. To systematically identify plasma proteins causally linked to BPH pathogenesis and therapeutic potential, we conducted a proteome-wide association study (PWAS) integrated with multi-omics analytical approaches.
Methods: Genome-wide association study (GWAS) datasets of bioavailable testosterone (BAT) and BPH were harmonized by multi-trait analysis of GWAS (MTAG) to enhance discovery power. Subsequent proteomic integration encompassed PWAS, two-sample Mendelian randomization (MR), and Bayesian colocalization analyses, complemented by pathway enrichment evaluation. Validation was performed using conventional BPH GWAS data.
Results: This integrative analysis identified 25 plasma proteins exhibiting significant associations with BPH risk (adjusted P<0.05), including two proteins (AIF1 and RSPO3) independently validated in the conventional BPH GWAS dataset. MR analyses established causal relationships for 18 proteins (adjusted P<0.05), with Bayesian colocalization confirming shared causal variants between BPH and key proteins AIF1 [posterior probability 4 (PP4) =0.999], RSPO3 (PP4 =0.714), and COL2A1 (PP4 =0.920). Pathway analysis revealed enrichment in inflammatory signaling and extracellular matrix remodeling.
Conclusions: This first PWAS investigation of BPH delineates a panel of circulating proteins with mechanistic and therapeutic implications, particularly highlighting AIF1 and RSPO3 as priority candidates for functional validation and drug development.
期刊介绍:
ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.