To investigate the biological function of these co-regulated modules, we looked for enrichment of gene ontology terms and involvement in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways among the genes in cis-eQTL clusters. Among the 10 major cis-eQTL clusters identified, we found evidence for significant enrichment of 60 gene ontology terms or KEGG pathways in 6 clusters (Supplementary Table 4). We found significant enrichment of cation-binding genes (gene ontology GO:0043169, cation binding; Benjamini-corrected modified Fisher’s exact P = 1.1 × 10−5) among genes targeted by the cerebellum-specific cis-eQTL cluster. This finding is in keeping with existing data suggesting that calcium homeostasis and, in particular, ITPR1-dependent signaling are central to Purkinje cell function and that disruption of this signaling system results in ataxia29. We identified six genes in this cluster that when disrupted are known to give rise to ataxia, including ITPR1 itself and CACNA1A. Thus, the cerebellum-specific regulation of these genes may provide an explanation for why, despite being ubiquitously expressed in human brain, mutations in these genes give rise to cerebellar ataxia. We also identified a significant enrichment
