Gene-based analyses in the AA data identified 3 genes that surpassed genome-wide correction (Psignificance = 2.76E-06, corrected for 18,125 protein coding genes; Supplemental Figure S7; Supplemental Table S3). The genes were SH3 Domain Binding Kinase Family Member 3 (SBK3; chromosome 19), DAZ Interacting Zinc Finger Protein 3 (DZIP3; chromosome 3) and CRK Like Proto-Oncogene, Adaptor Protein (CRKL; chromosome 22). DZIP3 and CRKL are ubiquitously expressed with appreciable expression in brain regions, while SBK3 is expressed in cardiac tissue (Supplemental Figure S8). Gene-set analyses did not identify any GO terms that surpassed multiple testing correction. We also performed gene function analyses with 26 genes that mapped to the region of 2 of the GWS loci (including, but not limited to SLITRK5, NPHP3 and NPHP3-AS1, LINC00433) on chromosomes 3 and 13. Two positional gene sets (MSigDB_c1) on chromosome 3 and one on chromosome 13 were significantly enriched for prioritized genes (chr3q22, Padjusted = 8.3E-10: NPHP3, NPHP3-AS1, BFSP2-AS1, SRPRB, C3orf36; chr3q21, Padjusted = 1.6E-4: TMEM108, BFSP2, TF; and chr13q31, Padjusted = 1.4E-09: SLITRK5, PEX12P1, KRT18P27). Of these, Transferrin (TF) in particular, showed higher average differential expression in brain tissue (Supplemental Figure S9).
