Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 1

Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease. Snap-frozen human substantia nigras (SNs) of 16 individuals with a clinicopathological diagnosis of incidental Lewy body (ILB) disease with Lewy bodies detected in the brainstem nuclei of locus coeruleus and substantia nigra, but generally not in higher cortical regions consistent with Braak stage 3 criteria for Parkinson's disease (PD), and 17 age-, sex-, postmortem interval-, and RNA integrity number-matched controls, who were clinicopathologically within normal limits for age collected under the rapid-autopsy program of Sun Health Research Institute or by the Harvard Brain Tissue Resource Center at McLean Hospital, were used for gene expression analyses in stage 2. Protocols were approved by the Institutional Review Board of Brigham and Women’s Hospital. RNA was isolated and quality-controlled as described by Agilent Bioanalyzer6. Only RNAs with preserved ribosomal peaks on electropherogram were forwarded for analysis, and RINs of cases and controls were matched. 350 ng of total RNA were reverse transcribed from each SN sample and hybridized to Illumina HumanHT-12v3 Expression BeadChips targeting more than 25,000 annotated genes with more than 48,000 probes derived from the National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq; Build 36.2, Rel 22) and UniGene (Build 99) databases, and scanned on a BeadArray Reader. Data were processed, normalized by “average normalization”, and quality-controlled using GenomeStudio. The supplementary file 'GSE20159_non-normalized.txt' contains non-normalized data for Samples GSM505716-GSM505748.