Extended Data Fig. 5: Comprehensive Analysis of Genetic Influence on Kidney pQTL/eQTL and eGFR GWAS.

(a) Illustration of the use of SMR and HEIDI tests to determine if the same genetic variants influence both kidney pQTL/eQTL and eGFR GWAS, suggesting potential causality. (b, c) Pie charts displaying the number of pQTL proteins and eQTL genes prioritized for their effects on eGFR were supported by SMR and HEIDI analysis, as well as those supported by SMR analysis alone, where HEIDI did not indicate a significant result. (d) Manhattan plot representing chromosomal locations (x-axis) and the strength of the SMR significance for eGFR GWAS, and human kidney pQTL expressed as -log10(SMR Pval) (y-axis). The top 25 most significant protein associations are labeled. The red dashed line represents the significance threshold (P = 6.44×10^-5, Methods). Blue dots denote significant associations in both SMR and HEIDI analyses, while grey dots indicate non-significant associations. (e, f) Venn diagrams illustrating (e) proteins and (f) genes showing significance in colocalization (coloc) and prioritized for their potential effects based on SMR and HEIDI analyses for eGFR GWAS. (g) Combined Venn diagram indicating the overlap between proteins and genes with significant coloc findings and those prioritized based on evidence from both SMR and HEIDI analyses. (h) The UpSet plot shows the overlap of significant proteins across coloc, SMR/HEIDI, and moloc analyses. Bars represent the number of overlapping proteins for each combination of analyses. SMR & HEIDI refers to proteins that are significant in both SMR and HEIDI analyses.