What is the clinical evidence from this study?

Study design: Cohort. Population: Fatty acid levels (n=2374). Intervention: Genetic variants (SNPs). Primary outcome: Association between genetic variants and 22 red blood cell fatty acids and 15 fatty acid ratios after adjusting for dietary covariates.

April 13, 2018Open Access

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort

Key Result

A genome-wide association study identified four novel and nine previously known genetic loci associated with red blood cell fatty acid levels and ratios after adjusting for dietary covariates.

Study Design

Type

Cohort (n=2,374)

Structured PICO

Population

2,374 individuals from the Framingham Heart Study Offspring Cohort who attended Examination 8 between 2005 and 2008, mean age 66.36 years, 45.33% male.

Outcome

Genetic variants associated with 22 red blood cell fatty acids and 15 fatty acid ratios after adjusting for dietary covariatessurrogate

Adjusting for dietary covariates in a genome-wide association study of red blood cell fatty acids identified four novel genetic loci, highlighting the complex genetic architecture of circulating fatty acid levels.

Limitations

Limited statistical power due to sample size
Complex correlation structure between fatty acids was not explicitly modeled
Use of self-reported dietary information via food frequency questionnaire
Inability to determine causality from association

Abstract

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.

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