This study utilized Mendelian randomization (MR) to investigate the impact of inflammatory proteins on knee osteoarthritis (KOA), measured using the ratio of protein levels (rQTLs). The primary objective was to identify potential intervention targets to mitigate KOA progression. Data from 2821 rQTLs, 91 inflammatory proteins, and KOA-related genetic variations were obtained through genome-wide association studies (GWAS). Bidirectional MR identified rQTLs with unidirectional causal relationships with KOA. Further analyses included false discovery rate (FDR) correction, colocalization, and mediation analysis. Two inflammatory proteins were found to be associated with KOA: T-cell surface glycoprotein CD5 [OR (95% CI) = 0.867 (0.760–0.990), P_IVW = 0.035] and C-X-C motif chemokine 9 [OR (95% CI) = 1.150 (1.001–1.320), P_IVW = 0.048]. Variations in their levels influenced rQTLs, producing differential effects on KOA. Specifically, rQTL-ANGPTL3/TFPI (human recombinant angiopoietin-like protein 3/Tissue factor pathway inhibitor) was identified as a mediator in the effect of T-cell surface glycoprotein CD5 levels on KOA. T-cell surface glycoprotein CD5 levels were negatively correlated with rQTL-ANGPTL3/TFPI (β1 = −0.084), while rQTL-ANGPTL3/TFPI was positively correlated with KOA (β2 = 0.159). These findings align with the total effect, where T-cell surface glycoprotein CD5 levels were negatively associated with KOA (β = −0.143). Thus, rQTL-ANGPTL3/TFPI may serve as a reliable mediator in the pathway through which T-cell surface glycoprotein CD5 levels affect KOA. This mediator may not only represent a potential therapeutic target but also serve as a biomarker for assessing KOA treatment efficacy, offering a novel direction for KOA diagnosis and management.

Objective: This study aimed to investigate the role of the gut microbiome in androgenetic alopecia (AGA) among obese individuals using Mendelian randomization (MR), and to identify potential therapeutic targets for mitigating AGA in this population. Methods: Genomic data for 412 gut microbiomes, AGA, and obesity were obtained from genome-wide association studies (GWAS). Bidirectional MR was performed using inverse variance weighted (IVW) as the primary analysis method, complemented by sensitivity analyses. Potential therapeutic targets within the gut microbiome associated with AGA in obese individuals were identified. Results: Two gut microbiomes were identified as having a significant impact on obese individuals with AGA. Specifically, the abundance of the sulfoglycolysis pathway in gut bacteria was found to significantly increase the risk of both obesity and AGA. In contrast, the abundance of the de novo biosynthesis of the adenosine ribonucleotide pathway in gut bacteria was associated with a significant increase in the risk of obesity but a significant decrease in the risk of AGA. Conclusions: The abundance of gut bacterial pathways, including sulfoglycolysis and the de novo biosynthesis of adenosine ribonucleotides, can serve as potential therapeutic targets for managing obesity-associated AGA. These findings offer a novel research direction for the development of innovative diagnostic and treatment strategies for patients with obesity and AGA.