Journal Article

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

Veenstra, Jenna, Vander Woude, Jason, Harris, William S., Westra, Jason, Shearer, Greg C., Fischer, Karen, Tintle, Nathan L., Disselkoen, Craig, Koch, Kristin, Kalsbeek, Anya, O’Bott, Jacob, McKenzie, Katelyn A.

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / Blood / Blood lipids / Chromosome 14 / Chromosome 7 / Cohort Studies / Composition / Computer science / Consortia / Desaturase / Diet / Eicosapentaenoic acid / Epistasis / Erythrocytes / Erythrocytes - metabolism / Fatty acids / Fatty Acids - metabolism / Female / Gene expression / Genes / Genetic aspects / Genetic Association Studies / Genetic diversity / Genetic Loci / Genetic variance / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genotype-environment interactions / Genotypes / Health aspects / Heart / Humans / Loci / Male / Mathematics / Medicine and Health Sciences / Metabolism / Offspring / Polymorphism, Single Nucleotide / Proteins / Ratios / Red blood cells / Schizophrenia