Fig. 4

Association results of CSF sTREM2 at chromosome 3 and in vitro functional validation using PBMC-derived macrophages. A Forest plots of effect size estimated by cohort for rs73823326. The effect allele is T for rs73823326. Heterogeneity P is 0.75 for rs73823326. B Violin plots of CSF sTREM2 Z-Score Residuals by genotypes of rs73823326. C UCSC genome browser visualization of Microglia and Neurons specific assay for transposase-accessible chromatin with sequencing (ATAC-seq), H3K27ac Chromatin immunoprecipitation followed by sequencing (ChiP-seq), H3K4me3 ChiP-seq and proximity ligation-assisted ChIP-Seq (PLAC-seq) loops at the chr 3 RBMS3 – TGFBR2 locus. Chromatin loops linking the promoter of TGFBR2 to active gene-regulatory region close to rs73823314 (LD r2=1 with rs73823326 and P=2.54 x 10^-8) is specific in microglia. D Quantification of intracellular TGFBR2 (left panel), TREM2 (middle panel) and extracellular sTREM2 protein levels in PBMC-derived macrophages upon TGFBR2 overexpression. E Quantification of intracellular RBMS3 (left panel), TREM2 (middle panel) and extracellular sTREM2 protein levels in PBMC-derived macrophages upon RBMS3 overexpression. n = 15 from 4 independent experiments. F Quantification of intracellular TGFBR2 (left panel), TREM2 (middle panel) and extracellular sTREM2 (right panel) protein levels in PBMC-derived macrophages upon TGFBR2 knockdown. n = 9 from 3 independent experiments. ns: not significant, ** p < 0.01, **** p < 0.0001. Results are shown in mean ± SEM