Most genome-wide association studies interested in fatty acids have explored relationships between genetic variants and plasma phospholipid fatty acid proportions, but few have utilized membrane fatty acid profile of red blood cells (RBC) and even fewer have accounted for lifestyle covariates such as diet. Recently, using RBC fatty acid data from the Framingham Offspring Study, over 2.5 million single nucleotide polymorphisms (SNPs) were tested for association with 14 RBC fatty acids. In that analysis, 191 different SNPs were found to be associated with at least one fatty acid. We now report on an updated analysis which includes adjustments for dietary covariates and additional fatty acids, which has identified novel loci. In additional to single marker analyses, we also report on the results of gene based testing approaches and another novel approach using a mixture of normal distributions to assist in directly tying fatty acid levels to particular genotypes.