Genome-wide association study of Red Blood Cell fatty acids in the Women's Health Initiative Memory Study

Abstract

Despite their widespread associations with a wide variety of disease phenotypes, the genetics of red blood cell fatty acids remains understudied. We present one of the first genome-wide association studies of red blood cell fatty acid levels, using the Women's Health Initiative Memory study – a prospective cohort of N = 7,479 women aged 65–79. Approximately 9 million SNPs were measured directly or imputed and, in separate linear models adjusted for age and genetic principal components of ethnicity, SNPs were used to predict 28 different fatty acids. SNPs were considered genome-wide significant using a standard genome-wide significance level of p < 1 × 10–8. Twelve separate loci were identified, seven of which replicated results of a prior RBC-FA GWAS. Of the five novel loci, two have functional annotations directly related to fatty acids (ELOVL6 and ACSL6). While overall explained variation is low, the twelve loci identified provide strong evidence of direct relationships between these genes and fatty acid levels. Further studies are needed to establish and confirm the biological mechanisms by which these genes may directly contribute to fatty acid levels.