Macrophage-specific <i>trans</i>-eQTL colocalized in Parkinson’s disease associated CTSB locus.

Abstract

(A) The genotype for Parkinson’s disease susceptibility allele rs1296028 is significantly associated with the individual scores of CG component 46. The rs1296028 affects the expression of 16 genes in component 46 in macrophage (CG) (left panel). Tissue specificity scores suggest CG component 46 is active in macrophage (Right). P-value: ***: trans-eGenes with PIP > 0.5 and 2.5% distributional cut-off (green dotted line) are shown. Trans-eQTL associations that replicated (FDR CTSB). The beta coefficients from Mendelian randomization analysis are shown for the significant trans-eGenes. (D) Experimental validation using THP-1 derived macrophages. CTSB was knocked-down using siRNA during 48 h and the levels of the top-scoring genes in the component were measured by qPCR. Data was normalized against scramble siRNA (SCR). P-value: *: <0.05 | ***: <0.001.</p