|KELLY, JENNIFER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|DASHTI, HASSAN - Harvard University|
|ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|MATUSZEK, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|HUGGINS, GORDON - Tufts Medical Center|
|BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Current Developments in Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2019
Publication Date: 6/13/2019
Citation: Kelly, J.M., Dashti, H.S., Ordovas, J.M., Matuszek, G., Smith, C.E., Huggins, G., Booth, S.L. 2019. Associations of lipid-related SNPs with circulating phylloquinone are proportional with triglycerides. Current Developments in Nutrition. 3(Suppl_1). Abstract No. P15-008-19. https://doi.org/10.1093/cdn/nzz037.P15-008-19.
Technical Abstract: Objectives: Phylloquinone is transported on triglyceride-rich lipoproteins. Preliminary evidence from a genome-wide association meta-analysis suggests that genetic variants that influence triglycerides (TGs), such as rs964184 at the APOA1/C3/A4/A5 gene cluster, also influence circulating phylloquinone. To further evaluate this overlap, we examined the linear relationship between a weighted TG genetic risk score (wTG-GRS) with circulating phylloquinone. Methods: We constructed a wTG-GRS comprised of 20 SNPs that were previously associated with TGs in a genomewide association meta-analysis for blood lipids (n >188,000 individuals of European ancestry). The assigned weights corresponded to the effect-sizes (beta) reported for each SNP's association with TGs. With meta-analytic summary statistic data from a separate genome-wide association meta-analysis of circulating phylloquinone (n=2,138 individuals of European ancestry), a statistical technique was used to approximate the linear association of the wTG-GRS with circulating phylloquinone. A p-value of 0.05 for the estimate was considered statistically significant. First, the estimate was calculated without adjustment for TGs using Model 1 summary statistics, then calculated with adjustment for TGs using Model 2 summary statistics. Results: The estimate for the linear association of the wTG-GRS with circulating phylloquinone was significant without and with adjustment for TGs (Model 1: beta=0.052, p=< 0.0001, Model 2: beta =0.027, p=0.0001, respectively). The goodness-of-fit of the model was improved from Model 1 (p-het=0.022) to Model 2 (p-het=0.054). Conclusions: The associations of TG-related SNPs with circulating phylloquinone were proportional to their associations with TGs. This provides further evidence of the shared genetic links between TGs and phylloquinone and suggests genetic studies of vitamin K should consider TGs.