Another negatively correlated module M47 was enriched for endothelial cell markers and genes involved in functions and disorders that relate to the immune response and oxygen transport in blood. One previous case-control study showed that anemia or low hemoglobin levels may precede the onset of PD37. Several studies using blood transcriptomic meta-analysis revealed genes associated with hemoglobin and iron metabolism were downregulated in PD patients compared to controls38–40. In our study, several hemoglobin genes (HBD, HBB, HBA1, HBA2, and OASL) were also present in module M47 of which HBD and HBB have been described to be highly interconnected with SNCA40. We also found an association between the interferon-gamma-mediated signaling pathway and M47 in which OASL also plays a role. Module M47 was negatively co-expressed with SNCA. Notably, a significant loss of negative co-expression between SNCA and interferon-gamma genes in the substantia nigra has been demonstrated in PD patients as compared to controls41. This loss may result from a downregulation of genes within M47 in the substantia nigra of PD patients, similarly as was observed in blood transcriptomics of PD38–40. This
