rs16969681

This functional genomics study identifies two SNP-containing enhancer elements in the chromosome 15q13.3 GWAS region associated with colorectal cancer risk. The SNPs rs1406389 (A allele) and rs16969681 modulate activity of distinct enhancers that regulate GREM1 gene expression, a BMP antagonist critical to colorectal epithelial homeostasis, with rs1406389 showing allele-specific enhancer activity and eQTL correlation with GREM1 expression in colon tissue.

Multicenter case-control study of 1,955 Brazilian individuals examining the WNT5A rs566926 polymorphism in non-syndromic orofacial cleft (NSOC). The C allele was significantly associated with cleft lip only (NSCLO), increasing risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). Multiple epistatic interactions were detected between rs566926 and variants in BMP4, GREM1, and FGFR1, with strongest effects in individuals of European ancestry.

This case-control study in Japanese population evaluated CRC risk prediction models using SNPs identified in European and East Asian GWAS. An 11-SNP model combining 6 European-identified SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) with 5 East Asian-identified SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) showed significantly improved discrimination capacity compared to a 6-SNP model alone (derivation AUC 0.6392 vs 0.6125, P=0.0039; replication AUC 0.5695 vs 0.5310, P=0.0018), with cumulative risk at age 80 estimated at 13% in high-risk versus 6% in low-risk genetic groups.