Genome-Wide Association Study of Plasma N6 Polyunsaturated Fatty Acids within the CHARGE Consortium.

BACKGROUND: Omega-6 (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 biologic pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with five plasma n6 PUFAs in 8,631 Caucasian adults (55% female) across five prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linoleic acid (DGLA), arachidonic acid (AA), and adrenic acid (AdrA) were expressed as % of total fatty acids. We performed linear regression with robust standard errors to test for SNP-fatty acid associations, with pooling using inverse-variance weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118, p-value = 8.1x10(-9); near NRBF2); on chromosome 16 with LA, GLA, DGLA, and AA ( rs16966952, p-value = 1.2×10(-15), 5.0×10(-11), 7.6×10(-65), and 2.4×10(-10), respectively; NTAN1); and on chromosome 6 with AdrA following adjustment for AA (rs3134950, p-value = 2.1×10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and AA, and further observed novel genome-wide significant association of this cluster with GLA, DGLA, and AdrA (p-value = 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.