An intronic variant in the GCKR gene is associated with multiple lipids

Previous studies have shown that an intronic variant rs780094 of the GCKR gene (glucokinase regulatory protein) is significantly associated with several metabolites, but the associations of this genetic variant with different lipids is largely unknown. Therefore, we applied metabolomics approach to measure metabolites in a large Finnish population sample (METSIM study) to investigate their associations with rs780094 of GCKR. We measured metabolites by mass spectrometry from 5,181 participants. P < 5.8 × 10^-5 was considered as statistically significant given 857 metabolites included in statistical analyses. We found novel negative associations of the T allele of GCKR rs780094 with serine and threonine, and positive associations with two metabolites of tryptophan, indolelactate and N-acetyltryptophan. Additionally, we found novel significant positive associations of this genetic variant with 12 glycerolipids and 19 glycerophospholipids. Significant negative associations were found for three glycerophospholipids (all plasmalogen-cholines), and two sphingolipids. Significant novel associations were also found with gamma-glutamylthreonine, taurocholenate sulfate, and retinol. Our study adds new information about the pleiotropy of the GCKR gene, and shows the associations of the T allele of GCKR rs780094 with lipids.