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Am J Clin Nutr. 2019 Jan 1;109(1):176-185. doi: 10.1093/ajcn/nqy298.

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

Author information

Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
CHU de Québec Research Center-Endocrinology and Nephrology, Quebec City, Quebec, Canada.
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
NIHR Southampton Biomedical Research Center, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom.
Norwich Medical School, University of East Anglia, Norwich, United Kingdom.



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 < 0.0001). Nonresponders to the n-3 FA supplementation had a higher GRS than did responders. In the FINGEN replication study, the GRS explained 3.67% of TG response variance (P = 0.0006).


Fine mapping proved to be effective to refine the previous GRS. Carrying increasing numbers of at-risk alleles of 31 SNPs confers a higher risk of being nonresponsive to n-3 FAs. The genetic profile therefore appears to be an important determinant of the plasma TG response to an n-3 FA supplementation and could be used to target those most likely to gain clinical benefit. This trial was registered at as NCT01343342.

[Available on 2020-01-01]
[Indexed for MEDLINE]

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