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Chunk #39 — Discussion

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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease.
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is high (median correlation 0.68, Figure S21), and as high or higher than correlations across methods within cell type and species (single-cell vs single-nuclei RNA-seq, median correlation 0.6) 53. (D) We evaluated protein-coding genes with 1:1 orthologs between mouse and human. These constitute most human protein-coding genes, and these genes are generally highly conserved particularly in the nervous system. We did not study genes present in one species but not in the other. (E) More specifically, we previously showed that gene expression data cluster by cell type and not by species 12, indicating broad conservation of core brain cellular functions across species. (F) We used a large number of genes to map cell types to traits (~1500 genes for each cell type), minimizing potential bias due to individual genes differentially expressed across species. (G) If there were strong differences in cell type gene expression between mouse and human, we would not expect that specific genes in mouse cell types would be enriched in genetic associations with human disorders. However, it remains possible that some cell types have different gene expression patterns between mouse and human, are only present in one species, have a different function or are involved in different