Supplementary Materials

The PDF file includes:

  • Fig. S1. CSF sTREM2 is highly correlated with age and CSF tau.
  • Fig. S2. CSF sTREM2 concentration is higher in carriers of TREM2 p.R47H than elderly nondemented individuals.
  • Fig. S3. The MS4A gene region is associated with CSF sTREM2 in a GWAS.
  • Fig. S4. The association of MS4A with sTREM2 is driven by both AD cases and controls.
  • Fig. S5. No common variants that pass multiple test correction were found to be associated with sTREM2 in the ADAM17, ADAM10, TREM2, or APOE gene regions.
  • Fig. S6. TREM2, MS4A4A, MS4A6A, and MS4A7 brain mRNAs are highly correlated in AD cases and controls.
  • Fig. S7. The correlation of TREM2, MS4A4A, MS4A6A, and MS4A7 brain mRNA replicates in independent cohorts.
  • Fig. S8. The correlation of TREM2, MS4A4A, MS4A6A, and MS4A7 brain mRNA is found in multiple cortical areas.
  • Fig. S9. Cell-based studies indicate that MS4A4A, but not MS4A6A, regulates sTREM2 concentrations.
  • Fig. S10. Silencing of MS4A4A leads to a decrease in sTREM2.
  • Table S1. ADNI CSF cohort characteristics.
  • Table S3. Epidemiological characteristics for the replication datasets.
  • Table S4. Results from individual single-variant analyses of replication datasets for rs1582763 and rs6591561.
  • Table S5. Braineac cis-eQTL results for rs6591561 (uncorrected P < 0.001) in average all regions (aveALL), frontal cortex (FCTX), hippocampus (HIPP), and temporal cortex (TCTX).
  • Table S6. Braineac cis-eQTL results for rs1582763 (uncorrected P < 0.001) in average all regions (aveALL), frontal cortex (FCTX), hippocampus (HIPP), and temporal cortex (TCTX).
  • Table S7. Gene expression correlation results from Knight ADRC and DIAN RNA-seq analyses, testing TREM2 expression against MS4A4A or MS4A6A.
  • Table S8. Gene expression correlation results from Mayo RNA-seq analyses from temporal cortex, testing TREM2 expression against MS4A4A or MS4A6A.
  • Table S9. Gene expression correlation results from Mount Sinai Brain Bank RNA-seq analyses from Brodmann areas 36 or 44, testing TREM2 expression against MS4A4A or MS4A6A.

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Other Supplementary Material for this manuscript includes the following:

  • Table S2 (Microsoft Excel format). Functional annotation for all variants with a suggestive association (P < 1 × 10−5) with CSF sTREM2.
  • Data file S1 (Microsoft Excel format). Individual-level data for Fig. 5 and figs. S9 and S10.