Fifty-one novel, replicated loci identified in genome-wide association study of polyunsaturated and monounsaturated fatty acids in 124,024 European individuals
Francis, M.; Sun, Y.; Xu, H.; Brenna, J. T.; Ye, K.
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Circulating polyunsaturated and monounsaturated fatty acid (PUFA and MUFA) levels, whose imbalances co-occur with human metabolic diseases, have strong heritable components. We performed the largest genome-wide association study (GWAS) to-date on fourteen PUFA and MUFA phenotypes, measured by nuclear magnetic resonance in plasma. We identified 612 significant locus-phenotype associations (115 unique loci; P < 1.678x10-8) in a European cohort from UK Biobank (UKB-EUR; n=101,729). Replication of five phenotypes (omega-3, omega-6, DHA, LA, MUFAs) was conducted in two external European studies: FinMetSeq (n=8,751) and a meta-analysis by Kettunnen et al. (n=3,644-13,544). Meta-analysis of these three studies yielded 254 significant locus-phenotype associations (109 unique loci; P < 2.439x10-8); we identified 87 novel loci, 51 of which were replicated. A transcriptome-wide association study of the UKB-EUR cohort revealed an additional twelve novel loci. This study improves our understanding of the genetic architecture of unsaturated fatty acids and can inform future genotype-based dietary interventions.
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