Our group built a genetic risk score (GRS) of the plasma triglyceride (TG) response to an omega-3 (n-3) fatty acid (FA) supplementation in Caucasian Canadians that explained 21.53% of the TG variance. The objective was to refine the GRS by fine mapping and to test its association with the TG response in young Mexican adults. A total of 191 participants underwent a 6-week n-3 FA supplementation providing 2.7g/day of docosahexaenoic and eicosapentaenoic acids. Using quantitative polymerase chain reaction (PCR), 103 single-nucleotide polymorphisms (SNPs) were genotyped. A stepwise regression adjusted for age, sex, and body mass index (BMI) was used to select the strongest SNPs to include in the genetic risk model. A GRS was calculated from the sum of at-risk alleles. The contribution of the GRS to the TG response was assessed by ANCOVA with age, sex, and BMI included in the model. Several differences in allele frequency were observed between Canadians and Mexicans. Five lead SNPs were included in the genetic risk model, in which the GRS accounted for 11.01% of the variance of the TG response (p < 0.0001). These findings highlight the important contribution of genetic factors to the heterogeneity of the TG response to an n-3 FA supplementation among Mexicans.