Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation

Using a genome-wide association study (GWAS) approach, our group previously computed a genetic risk score (GRS) from single nucleotide polymorphisms (SNPs) of 10 loci that affect the plasma triglyceride (TG) response to an omega-3 (n–3) fatty acid (FA) supplementation. The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants. A total of 208 participants of the Fatty Acid Sensor (FAS) Study received 5 g fish oil/d, containing 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexanoic acid, for 6 wk. Plasma TG concentrations were measured before and after supplementation. Dense genotyping and genotype imputation were used to refine mapping around GWAS hits. A GRS was computed by summing the number of at-risk alleles of tagging SNPs. Analyses were replicated in samples of the FINGEN study. A total of 31 tagging SNPs associated with the TG response were used for GRS calculation in the FAS study. In a general linear model adjusted for age, sex, and body mass index, the GRS explained 49.73% of TG response variance (P