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Meta-Analysis
.2014 Jun;7(3):321-331.
doi: 10.1161/CIRCGENETICS.113.000208. Epub 2014 May 13.

Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium

Affiliations
Meta-Analysis

Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium

Weihua Guan et al. Circ Cardiovasc Genet.2014 Jun.

Abstract

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.

Keywords: N6 fatty acids; epidemiology; genome-wide association study; polyunsaturated fatty acids.

© 2014 American Heart Association, Inc.

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Figures

Figure 1
Figure 1
N6 polyunsaturated fatty acid metabolic pathway and summary of genome-wide significant associations. The associations of loci with each fatty acid are shown with dashed arrows. + and – signs indicate the direction of the associations.
Figure 2A-E
Figure 2A-E
Meta-analysis of genome-wide associations with n6 polyunsaturated fatty acids:A. Linoleic acid (LA; 18:2,n6),B. Gamma linolenic acid (GLA; 18:3,n6),C. Dihomo-gamma-linolenic acid (DGLA; 20:3,n6),D. Arachidonic acid (AA; 20:4,n6),E Adrenic acid (AdrA; 22:4,n6). Associations were graphed by chromosome position and –log10 (p-value) up to p-values of 10−10. Triangles indicate additional SNPs with p-values < 10−10. Genes of interest within the significant SNPs are indicated.
Figure 2A-E
Figure 2A-E
Meta-analysis of genome-wide associations with n6 polyunsaturated fatty acids:A. Linoleic acid (LA; 18:2,n6),B. Gamma linolenic acid (GLA; 18:3,n6),C. Dihomo-gamma-linolenic acid (DGLA; 20:3,n6),D. Arachidonic acid (AA; 20:4,n6),E Adrenic acid (AdrA; 22:4,n6). Associations were graphed by chromosome position and –log10 (p-value) up to p-values of 10−10. Triangles indicate additional SNPs with p-values < 10−10. Genes of interest within the significant SNPs are indicated.
Figure 2A-E
Figure 2A-E
Meta-analysis of genome-wide associations with n6 polyunsaturated fatty acids:A. Linoleic acid (LA; 18:2,n6),B. Gamma linolenic acid (GLA; 18:3,n6),C. Dihomo-gamma-linolenic acid (DGLA; 20:3,n6),D. Arachidonic acid (AA; 20:4,n6),E Adrenic acid (AdrA; 22:4,n6). Associations were graphed by chromosome position and –log10 (p-value) up to p-values of 10−10. Triangles indicate additional SNPs with p-values < 10−10. Genes of interest within the significant SNPs are indicated.
Figure 2A-E
Figure 2A-E
Meta-analysis of genome-wide associations with n6 polyunsaturated fatty acids:A. Linoleic acid (LA; 18:2,n6),B. Gamma linolenic acid (GLA; 18:3,n6),C. Dihomo-gamma-linolenic acid (DGLA; 20:3,n6),D. Arachidonic acid (AA; 20:4,n6),E Adrenic acid (AdrA; 22:4,n6). Associations were graphed by chromosome position and –log10 (p-value) up to p-values of 10−10. Triangles indicate additional SNPs with p-values < 10−10. Genes of interest within the significant SNPs are indicated.
Figure 2A-E
Figure 2A-E
Meta-analysis of genome-wide associations with n6 polyunsaturated fatty acids:A. Linoleic acid (LA; 18:2,n6),B. Gamma linolenic acid (GLA; 18:3,n6),C. Dihomo-gamma-linolenic acid (DGLA; 20:3,n6),D. Arachidonic acid (AA; 20:4,n6),E Adrenic acid (AdrA; 22:4,n6). Associations were graphed by chromosome position and –log10 (p-value) up to p-values of 10−10. Triangles indicate additional SNPs with p-values < 10−10. Genes of interest within the significant SNPs are indicated.
Figure 3A-C
Figure 3A-C
Regional association plots in the genome-wide association of Linoleic acid (LA; 18:2,n6). The color scheme is red for strong linkage disequilibrium (LD) and fading color for lower LD.A. Regional association plot for rs10740118 on chromosome 10.B. Regional association plot for rs174547 on chromosome 11.C. Regional association plot for rs16966952 on chromosome 16
Figure 3A-C
Figure 3A-C
Regional association plots in the genome-wide association of Linoleic acid (LA; 18:2,n6). The color scheme is red for strong linkage disequilibrium (LD) and fading color for lower LD.A. Regional association plot for rs10740118 on chromosome 10.B. Regional association plot for rs174547 on chromosome 11.C. Regional association plot for rs16966952 on chromosome 16
Figure 3A-C
Figure 3A-C
Regional association plots in the genome-wide association of Linoleic acid (LA; 18:2,n6). The color scheme is red for strong linkage disequilibrium (LD) and fading color for lower LD.A. Regional association plot for rs10740118 on chromosome 10.B. Regional association plot for rs174547 on chromosome 11.C. Regional association plot for rs16966952 on chromosome 16
Figure 4
Figure 4
Regional association plot on chromosome 6 in the secondary analyses, adjusting arachidonic acid (AA) for adrenic acid (AdrA). The color scheme is red for strong linkage disequilibrium (LD) and fading color for lower LD.
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