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Additional file 1 of Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer’s disease

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posted on 2024-01-04, 04:40 authored by Lihua Wang, Niko-Petteri Nykänen, Daniel Western, Priyanka Gorijala, Jigyasha Timsina, Fuhai Li, Zhaohua Wang, Muhammad Ali, Chengran Yang, Menghan Liu, William Brock, Marta Marquié, Mercè Boada, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Agustín Ruiz, Raquel Puerta, Adelina Orellana, Jarod Rutledge, Hamilton Oh, Michael D Greicius, Yann Le Guen, Richard J. Perrin, Tony Wyss-Coray, Angela Jefferson, Timothy J. Hohman, Neill Graff-Radford, Hiroshi Mori, Alison Goate, Johannes Levin, Yun Ju Sung, Carlos Cruchaga
Additional file 1: Fig. S1. Principal component plots of C2 vs C1 using HapMap Phase II as reference. Fig. S2. Quantile-quantile plot (Q-Q plot) of GWAS for CSF sTREM2 in European individuals (EUR-GWAS). Fig. S3. Manhattan plot and quantile-quantile plots (Q-Q plots) of GWAS for CSF sTREM2 in non-European individuals (nonEUR-GWAS) and meta-analyses of EUR GWAS and nonEUR GWAS. Fig. S4. Scatterplot of effect size across GWAS analyses at four index variants. Fig. S5. Association results of CSF sTREM2 at chromosome 11. Fig. S6. Locus plots of rs12664332 at chromosome 6 for CSF sTREM2 and AD. Fig. S7. Experimental design, representative western blots of TGFBR2 and RBMS3 overexpression and knockdown of TGFBR2 in PBMC-derived macrophages presented in Figure 4. Fig. S8. Box plots of CSF sTREM2 Z Score by APOE ε4 dosage for EURs A), and non-EURs B). Fig. S9. UCSC genome browser visualization of brain cell type specific ATAC-seq, H3K27ac ChiP-seq, H3K4me3 ChiP-seq and PLAC-seq loops at the chr 19 APOE locus. Fig. S10. Experimental design and representative western blots of NECTIN2 overexpression in PBMC-derived macrophages presented in Figure 5 Fig. S11. NECTIN2 knock-down experiments. Quantifications of intracellular NECTIN2 protein levels. The cells were transduced with NECTIN2 shRNAs using MOI of 1 in 6 independent batches (A, B, C, D, E and F) and MOI of 2 in 4 independent batches (H, I, J and K). Each batch includes 3-4 wells transduced with control shRNA and 3 wells transduced with target NECTIN2 shRNAs B and C. Fig. S12. Dot plots and circular plots of proteins associated with rs72918674 at chromosome 11 and rs11666329 at chromosome 19. Fig. S13. Scatter plots of CSF sTREM2 measured using MSD vs SomaScan in Knight ADRC. Fig. S14. Box plots of CSF sTREM2 Z Score by ethnicity and sex.

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