We report here biologically interesting GWS results from a case–control GWAS of Ca-HL. There was one GWS association signal at the CHRM3 locus in Yale-Penn 1 EAs, represented by rs115455482, rs74722579, and rs1938228 (all r2 ≥ 0.95 in EAs; rs115455482 is rare in AAs), with all three SNPs nominally significant in Yale-Penn 2 EAs. Only rs115455482 and rs74722579 were available in COGA, which when meta-analyzed with Yale-Penn 1 and 2 samples increased the significance of the association. We further evaluated the association of rs115455482 and rs74722579 with Ca-HL in the Yale-Penn 1 and 2, and COGA AA samples. The nominally significant association for rs74722579 (a common variant in both AAs and EAs) in the AA meta-analysis further supports the association. Cis-eQTL analysis of CHRM3 in brain showed the rs115455482*T risk allele to be associated with lower expression of CHRM3 in brain tissue THAL. Further co-expression analysis in large brain tissue expression datasets and mouse single neurons demonstrated a significant correlation between the expression of CHRM3 or its mouse homologous Chrm3, and that of three genes (GABRG2, CHRNA4, and HRH3) that have been shown to affect risk for psychotic disorders, including schizophrenia. Similar to CHRM3 itself, these are all biologically relevant.
