Genome-Wide Interaction Study of Omega-3 PUFAs and Other Fatty Acids on Inflammatory Biomarkers of Cardiovascular Health in the Framingham Heart Study.

Jenna Veenstra,Caren E Smith,Craig Disselkoen,Jason Westra,Nathan Tintle,Anya Kalsbeek

doi:10.3390/nu9080900

Abstract

Numerous genetic loci have been identified as being associated with circulating fatty acid (FA) levels and/or inflammatory biomarkers of cardiovascular health (e.g., C-reactive protein). Recently, using red blood cell (RBC) FA data from the Framingham Offspring Study, we conducted a genome-wide association study of over 2.5 million single nucleotide polymorphisms (SNPs) and 22 RBC FAs (and associated ratios), including the four Omega-3 FAs (ALA, DHA, DPA, and EPA). Our analyses identified numerous causal loci. In this manuscript, we investigate the extent to which polyunsaturated fatty acid (PUFA) levels moderate the relationship of genetics to cardiovascular health biomarkers using a genome-wide interaction study approach. In particular, we test for possible gene–FA interactions on 9 inflammatory biomarkers, with 2.5 million SNPs and 12 FAs, including all Omega-3 PUFAs. We identified eighteen novel loci, including loci which demonstrate strong evidence of modifying the impact of heritable genetics on biomarker levels, and subsequently cardiovascular health. The identified genes provide increased clarity on the biological functioning and role of Omega-3 PUFAs, as well as other common fatty acids, in cardiovascular health, and suggest numerous candidate loci for future replication and biological characterization.

Highlights

We primarily focused on Omega-3 (n3) and Omega-6 (n6) fatty acid (FA) for this study: eicosapentaenoic acid (EPA, n3), docosapentaenoic acid- n3 (DPA, n3), docosahexaenoic acid (DHA, n3), alpha-linoleic acid (ALA, n3), linoleic acid (LA, n6), gamma-linoleic acid (GLA, n6), dihomo-gamma-linoleic acid (DGLA, n6), arachidonic acid (AA, n6), docosapentaenoic acid-n6 (DPA, n6), docosatetranoic acid (DTA, n6), eicosadienoic acid (EDA, n6), and oleic acid (OA, n9)
Oleic acid (OA) was included in this study as an exploratory look into the impacts of Omega-9 FAs [26], because it is one of most common FAs, and because we have previously identified a number of genetic variants associated with it [2]
In subsequent discussion about the result, the biomarker levels are reported as pg/mL, and the FA levels are reported as percent composition

Summary

Introduction

Genome-wide association studies (GWAS) have been previously used to identify common single nucleotide polymorphisms (SNPs) associated with fatty acid (FA) levels [1,2].There have been studies showing correlations between FA levels, Omega-3 and Omega-6 FAs, and a variety of disease phenotypes and risk factors, including total mortality [3], acute coronary syndrome [4,5], serum lipid levels [6], cognitive function [7], brain size [8,9], and inflammatory biomarkers [10].Such biomarkers, including C-reactive protein, are known risk factors of cardiovascular disease [11].Though studies exist that examine the influence FAs have on inflammation, the understanding of the relationship remains incomplete. Genome-wide association studies (GWAS) have been previously used to identify common single nucleotide polymorphisms (SNPs) associated with fatty acid (FA) levels [1,2].There have been studies showing correlations between FA levels, Omega-3 and Omega-6 FAs, and a variety of disease phenotypes and risk factors, including total mortality [3], acute coronary syndrome [4,5], serum lipid levels [6], cognitive function [7], brain size [8,9], and inflammatory biomarkers [10]. Little is known as to how genetics might alter the optimal dietary FA intake for the individual

Methods

Results

Discussion

Conclusion