Establishing gene regulatory networks from Parkinson’s disease risk loci

Journal article

Farrow et al Supplementary tables:All oligonucleotides included in the synthesied library (Agilent), see phenotype abbreviation descriptors above table78 PD GWAS loci identified by Nalls et al 2019, and the number of elements tested per locus. Rows 82-95 show GWAS loci identified by Nalls et al that did not pass final QC, but were included in the library21 PARK genes and summary data on the number of eQTLS identified in the brain, associated with the expression of these PARK genesCoDeS3D output data highlighting all putative regulatory eQTLs associated with the expression of one or more of the PARK genes in brain cell-types and tissuesSummary data from Booms et al. highlighting putative regulatory SNPs in microgliaMPRA identified general enhancers, based on Z-score calculations (+/- 3SD)Allele specific enhancers (Elements excluded from allele-specific mpralm analysis due to insufficient barcode numbers for either the ref or alt alleleMean depletion rank score for each element (SNP) included in the MPRA oligonucleotide libraryFABIAN prediction analysis to identify which allele-specific regulatory elements may disrupt a transcription factor binding siteEpigenomic and regulatory annotations of the allele-specific and general enhancer sites, data obtained from HaploregCoDeS3D output data highlighting significant eQTLS for each of the allele-specific and general enhancer SNPs. Analysis was run across all tissues within the GTEx database and all Hi-C cell-types available (see doi: 10.1093/brain/awac022 for more details)Differentially expressed genes in the KOLF.21J iPSC line for three of the MPRA identified allele-specific enhancers (rs11646653, rs78222414, rs3815082). Gene expression is compared between 3 replicates of the edited clones vs. 9 replicates of the WT cell line.

Authors: Farrow, SL; Schierding, W; Gokuladhas, S; Golovina, E; Fadason, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Brain
• Volume: 145
• Issue: 7
• Pages: 2422-2435
• Publication date: 2022-01-25
• DOI: 10.1093/brain/awac022
• EISSN: 1460-2156
• ISSN: 0006-8950
• Language: English
• Keywords: Disease; Genotype; Regulation of gene expression; Medicine; Genome-wide association study; Locus (genetics); Single-nucleotide polymorphism; Quantitative trait locus; Genetic association; Parkinson's disease; Gene; Pathology; Biology; Gene regulatory network; Gene expression; Genetics; Expression quantitative trait loci