Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson’s disease heritability

Overview of approach and datasets used. This study compiled several brain-related genomic annotations reflecting tissue- and cell-type-specific activity, using data generated by the GTEx project,20 the Barres group21 and the Linnarsson group.22 These annotations, each of which varied in their cellular resolution, included: tissue-specific eQTLs (reflecting the effect of genetic variation on gene expression); tissue-specific co-expression networks (reflecting the connectivity of a gene to all other expressed genes in the tissue), and tissue- and cell-type-specific gene expression. All annotations were constructed in a binary format (1 if the SNP is present within the annotation and 0 if not). For annotations where the primary input was a gene, all SNPs with a minor allele frequency？>？5% within？±？100？kb of the transcription start and end site were assigned a value of 1. For more details of how each individual annotation was generated see Methods. Stratified LDSC was then used to test whether an annotation was significantly enriched for the common-SNP heritability of PD or SC