Genome-Wide Association Study of Plasma N6 Polyunsaturated Fatty Acids Within the Cohorts for Heart and Aging Research in Genomic Epidemiology ConsortiumCLINICAL PERSPECTIVE

Background— Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase ( FADS ) genes, determine the composition of n6 PUFAs. Methods and Results— To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), γ-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism–fatty acid associations, with pooling using inverse-variance–weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P =8.1×10 −9 ; near NRBF2 ), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P =1.2×10 −15 , 5.0×10 −11 , 7.6×10 −65 , and 2.4×10 −10 , respectively; NTAN1 ), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P =2.1×10 −10 ; AGPAT1 ). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid ( P =2.3×10 −72 , 2.6×10 −151 , and 6.3×10 −140 , respectively). Conclusions— Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.