rs174537

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.

A replication study in 21,004 Japanese and 1,203 Mongolian individuals demonstrated that rs174547 in FADS1/FADS2 is associated with plasma lipid profiles in Asian populations. In Japanese, the C allele was significantly associated with increased triglycerides (P=1.5×10⁻⁶, β=0.04 mg/dl per allele) and decreased HDL-C (P=0.03), while in Mongolians, the C allele was strongly associated with decreased LDL-C (P=2.6×10⁻⁶, β=-5.7 mg/dl per allele). The variable effects across populations despite similar genetic backgrounds suggest gene-environment interaction with dietary polyunsaturated fatty acid intake.