Therapeutic targets for diabetic kidney disease: proteome-wide Mendelian randomization and colocalization analyses

• DOI: 10.2337/figshare.24964149.v1
• Publication Date: 2024-01-11T23:02:12Z
• Authors: Wei Zhang; Leilei Ma; Qianyi Zhou; Tianjiao Gu; Xiaotian Zhang; Haitao Xing
• Keywords: Mendelian Randomization; Proteome; Colocalization; Druggability; Genome-wide Association Study; Linagliptin

<p dir="ltr"><a href="" target="_blank">At present, safe and effective treatment drugs are urgently needed for diabetic kidney disease (DKD). Circulating protein biomarkers with causal genetic evidence represent promising drug targets, which provides an opportunity to identify new therapeutic targets. Summary data from two quantitative trait loci (pQTL) studies: one involving 4,907 plasma proteins 35,559 individuals, the other encompassing 4,657 among 7,213 European Americans. statistics DKD were obtained a large genome-wide association study (3345 cases 2372 controls) FinnGen (3676 283,456 controls). Mendelian randomization (MR) analysis was conducted examine potential targets DKD. The colocalization utilized</a> detect whether exist shared variants. To enhance credibility of results, external validation conducted. Additionally, enrichment analysis, assessment druggability, protein-protein interaction (PPI) networks employed further enrich research findings. proteome-wide MR analyses identified 21 blood that may causally be associated Colocalization supported relationship between 12 DKD, confirming four these proteins, TGFBI affirmed through separate group datasets. These results indicate targeting could approach treating warrant clinical investigations.</p>