Four SNPs (rs13381619, rs9955626, rs1792658, and rs1792671) within SMAD2, one SNP within SMAD3 (rs41473580" genes_norm="4087;4088;4089;4092">rs41473580), two SNPs within SMAD4 (rs7229678 and rs9304407), and one SNP within SMAD7 (rs12956924) were significantly associated with susceptibility only to UC. rs13381619 within SMAD2, rs4147358 within SMAD3, rs9304407 within SMAD4, and rs12956924 within SMAD7 exhibited the strongest association (p < 0.001, p = 0.021, p = 0.005, and p = 0.001, respectively).
In this work, by deciphering the overlapping genes, crosstalking genes and pivotal regulators of both UC- and CRC-associated functional module pairs, we revealed a variety of genes (including FOS and DUSP1, etc.), transcription factors (including SMAD3 and ETS1, etc.) and miRNAs (including miR-155 and miR-196b, etc.) that may have the potential to complete the connections between UC and CRC.
Consistent with epidemiologic predictions, many IBD-associated loci demonstrate genome-wide significant associations to both CD and UC, notably, genes whose products function in the interleukin-23 pathway, and transcription factors, including NK2 transcription factor related, locus 3 (NKX2-3), SMAD3, STAT3, ZMIZ1, and c-REL.