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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

1
Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
2
CHU de Québec Research Center-Endocrinology and Nephrology, Quebec City, Quebec, Canada.
3
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
4
NIHR Southampton Biomedical Research Center, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom.
5
Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Abstract

Background:

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.

Objectives:

The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants.

Methods:

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.

Results:

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).

Conclusions:

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 http://www.clinicaltrials.gov as NCT01343342.

PMID:
30624603
PMCID:
PMC6358031
[Available on 2020-01-01]
DOI:
10.1093/ajcn/nqy298
[Indexed for MEDLINE]

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