Document Type

Article

Publication Date

11-2014

Department

Mathematics, Statistics, and Computer Science

Keywords

PUFA, apoA-I maturation, Oleic acid, Linoleic acid, Arachidonic acid, Glycerol‐lipids

Abstract

Most genome-wide association studies have explored relationships between genetic variants and plasma phospholipid fatty acid proportions, but few have examined apparent genetic influences on the membrane fatty acid profile of red blood cells (RBC). Using RBC fatty acid data from the Framingham Offspring Study, we analyzed over 2.5 million single nucleotide polymorphisms (SNPs) for association with 14 RBC fatty acids identifying 191 different SNPs associated with at least 1 fatty acid. Significant associations (p<1×10−8) were located within five distinct 1 MB regions. Of particular interest were novel associations between (1) arachidonic acid and PCOLCE2 (regulates apoA-I maturation and modulates apoA-I levels), and (2) oleic and linoleic acid and LPCAT3 (mediates the transfer of fatty acids between glycerolipids). We also replicated previously identified strong associations between SNPs in the FADS (chromosome 11) and ELOVL (chromosome 6) regions. Multiple SNPs explained 8–14% of the variation in 3 high abundance (>11%) fatty acids, but only 1–3% in 4 low abundance (<3%) fatty acids, with the notable exception of dihomo-gamma linolenic acid with 53% of variance explained by SNPs. Further studies are needed to determine the extent to which variations in these genes influence tissue fatty acid content and pathways modulated by fatty acids.

Source Publication Title

Prostaglandins, Leukotrienes and Essential Fatty Acids

Publisher

Elsevier

DOI

10.1016/j.plefa.2014.11.007

Download

Share

COinS