Abstract MP065: Genetic Loci Associated With Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway: A Meta-analysis of Genome-wide Association Studies From the Charge Consortium
Background Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and mono-unsaturated fatty acids that are synthesized via de novo lipogenesis (DNL) or obtained from the diet. Circulating levels of these fatty acids are linked to several diseases including diabetes and heart disease. Prior family and twin studies suggest high heritability of circulating levels, but potential genes involved are unknown.
Objective To carry out a Genome-Wide Association Study (GWAS) to investigate genetic determinants of circulating levels of these fatty acids.
Methods GWAS in 5 population-based cohorts (n=8,961) of European ancestry. Each study conducted linear regression analysis using an additive genetic model. All analyses were adjusted for age, sex, site of recruitment, and principal components to account for possible population genetic substructure where appropriate. Study-specific results were combined using inverse-variance weighted meta-analysis.
Results We found SNPs at 7 novel loci linked at GWA significance to levels of one or more of these fatty acids (Figure). Directionality is reported for minor alleles. SNPs in ALG14 were associated with higher levels of 16:0 (P=2.7x10-11) and lower levels of 18:0 (P=2.7x10-11). SNPs in FADS1/2 were associated with higher 18:1n-9 (P=2.2x10-32) and 16:1n-7 (P=6.6x10-13), and lower 18:0 (P=1.3x10-20). SNPs in LPGAT1 were associated with lower 18:0 (P=2.8x10-9). SNPs in GCKR (P=9.8x10-10) and HIF1AN (P=5.7x10-9) were associated with higher 16:1n-7, whereas those in PKD2L1 (P=5.7x10-15) and another locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7.
Conclusion Our findings provide novel evidence that common variations in genes with diverse functions, including protein glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose- and oxygen-sensing pathways, are associated with circulating levels of fatty acids in the DNL pathway.
- © 2012 by American Heart Association, Inc.