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Chunk #7 — Results — PD Braak stage-related genes

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Transcriptomic signatures of brain regional vulnerability to Parkinson's disease.
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Since the expression patterns of the 960 BRGs were observed in only six non-neurological brains from the AHBA, we used two independent datasets from non-neurological controls for validation. For each dataset we assessed whether BRGs were also differentially expressed between regions related to the most distant Braak stages, and whether the decreasing or increasing expression patterns could be replicated. First, using microarray data from 134 individuals in the UKBEC20, we selected brain samples corresponding to the myelencephalon (R1), substantia nigra (R3), temporal cortex (R5), and frontal cortex (R6). For the 885 BRGs present in UKBEC, 139 out of 314 (44.3%) negatively correlated BRGs and 400 out of 571 (70.1%) positively correlated BRGs were differentially expressed between R1 and R6 (|FCR1–R6| > 1, BH-corrected P < 0.05, t-test). The mean expression of negatively and positively correlated BRGs showed indeed decreasing and increasing expression patterns, respectively, across regions R1, R3, R5, and R6 (Fig. 2d). Second, we used RNA-sequencing (RNA-seq) data from 88–129 individuals in the GTEx consortium19 and selected samples of the substantia nigra (R3), amygdala (R4), anterior cingulate cortex (R5),