Interactions between sugar-sweetened beverage consumption and genetic variants in the chREBP locus on lipoprotein concentrations in the UK biobank: a replication study

Authors: GUIRETTE, MELANIE - Tufts University; HASLAM, DANIELLE - Brigham & Women'S Hospital; PELOSO, GINA - Boston University; PITSILLIDES, ACHILLEAS - Massachusetts General Hospital; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DUPUIS, JOSEE - Boston University; DASHTI, HASSAN - Harvard University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HERMAN, MARK - Duke University; MCKEOWN, NICOLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Current Developments in Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 2/20/2020
Publication Date: 5/29/2020
Citation: Guirette, M., Haslam, D.E., Peloso, G.M., Pitsillides, A., Smith, C.E., Dupuis, J., Dashti, H.S., Lichtenstein, A.H., Herman, M.A., McKeown, N.M. 2020. Interactions between sugar-sweetened beverage consumption and genetic variants in the chREBP locus on lipoprotein concentrations in the UK biobank: a replication study. Current Developments in Nutrition. 4(Suppl_2):1255. https://doi.org/10.1093/cdn/nzaa058_013.
DOI: https://doi.org/10.1093/cdn/nzaa058_013

Interpretive Summary:

Technical Abstract: Objectives: A meta-analysis of 11 CHARGE cohorts (N=63,599) suggested that genetic variants within or near the CHREBP locus may modify the associations between sugar sweetened beverage (SSB) consumption and high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. The study objective was to replicate these findings in a large independent cohort. Methods: Blood lipids and 24-hour recalls were available for 57,794 adults of European ancestry in the UK Biobank (2006-'10). SSBs included "squash" and "fizzy" drinks derived from a single 24-hr recall. A total of 875 SNPs within or near the CHREBP locus were identified and included in this analysis. Associations between these SNPs and HDL-C and TG concentrations were quantified among participants who did not report SSB consumption (non-consumers, n=45,866), reported >/=0.5 servings/day of SSB (consumers, n=11,928), and a subset of consumers who reported >/=2 servings/day of SSB (high consumers, n=3,742). Interaction between SSB and selected SNPs on HDL-C and TG concentrations was evaluated by examining the difference in beta coefficients between strata. Results were considered statistically significant at a Bonferroni-corrected pinteract < 0.0001 (0.05/499 effective tests). Results: A significant interaction between SSB consumption and TBL2-rs71556729 on HDL-C concentration previously observed in the meta-analysis was replicated in UK Biobank. However, we observed a stronger interaction for a SNP in high linkage disequilibrium (R^2 = 0.93) FZD9-rs34821369 (MAF=0.03, pinteract = 8.2E-05) with TBL2-rs71556729 (MAF=0.03, pinteract = 0.0004). Among only SSB consumers, each additional minor G allele at FZD9-rs34821369 was associated with mean HDL-C concentrations 1.63 mg/dL (SE=0.53, p=0.002) higher than those with the major T allele. Conclusions: Our results suggest that adults with the minor allele at FZD9-rs34821369 may be protected against SSB-induced low HDL-C concentrations. These results are consistent the findings from a prior meta-analysis of 11 cohorts.