For each GWAS summary statistics, we excluded any SNPs with INFO score <0.6, with MAF < 1% or with estimated odds ratio > 25 or smaller than 1/25, the MHC region (chr6:25–34 Mb) for all GWAS and the APOE region (chr19:45020859–45844508) for the Alzheimer’s GWAS. We set a window of 35kb upstream to 10kb downstream of the gene coordinates to compute gene-level association statistics and used the European reference panel from the phase 3 of the 1000 genomes project 92 as the reference population. For each trait, we then used MAGMA to test whether the 10% most specific gene in each tissue/cell type was associated with gene-level genetic association with the trait. Only genes with at least 1TPM or 1 UMI per million in the tested cell type were used for this analysis. The significance level of the different cell types was highly correlated with the effect size of the cell type (Figure S25) with values ranging between 0.999 and 1 across the 18 brain related traits in the Zeisel et al. dataset 93. The significance threshold was set to a 5% false discovery rate across all tissues/cell types and traits within each dataset.
