We used publicly available eQTL datasets for liver39, cortex40 and Epstein-Barr virus-transformed lymphoblastoid cell lines41 to explore additional possible causal mechanisms testing for association between replicated loci and mRNA expression levels of nearby genes (Online Methods). The lead SNP in FADS1, rs174550, is in strong LD (r2=0.80) and close proximity (130 bp) to rs174548, a SNP highly associated with FADS1 mRNA expression levels in liver (P=1.7×10−5) and with FADS2 mRNA expression levels in lymphoblastoid cells (P=3.1×10−4). SNP rs174548 has also been associated (up to P=4.5×10−8) with a number of serum glycerophospholipid concentrations in a GWAS investigating metabolomic profiles42 and rs174550 also demonstrated strong associations (P<5.2×10−7) with the same metabolites (data not shown). These results are substantiated by previous work associating SNPs in this region with the fatty acid composition of phospholipids43. The latter suggest the minor allele variant of rs174550 results in a reduced efficiency of the fatty acid delta-5 desaturase reaction42. Finally, bioinformatic analysis identifies a perfect proxy, rs174545 (r2=1 with rs174550), whose glucose-raising allele abolishes a predicted miR-124 target site (see Online Methods). Taken together, these data support
