Sugar-sweetened beverage consumption may modify associations between genetic variants in the CHREBP locus and HDL-C and TG concentrations

Authors: HASLAM, DANIELLE - Harvard University; PELOSO, GINA - Boston University; GUIRETTE, MELANIE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; IMAMURA, FUMIAKI - University Of Cambridge; BARTZ, TRACI - University Of Washington; PITSILLIDES, ACHILLEAS - Boston University; WANG, CAROL - University Of Western Australia; LI-GAO, RUIFANG - Leiden University; WESTRA, JASON - Dordt College; PITKANEN, NIINA - University Of Turku; YOUNG, KRISTIN - University Of North Carolina; GRAFF, MARIAELISA - University Of North Carolina; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); BRAUN, KIM - Erasmus Medical Center; LUAN, JIAN'AN - University Of Cambridge; KAHONEN, MIKA - University Of Tampere; KIEFTE-DE JONG, JESSICA - Erasmus Medical Center; GHANBARI, MOHSEN - Erasmus Medical Center; TINTLE, NATHAN - Dordt College; LEMAITRE, ROZENN - University Of Washington; MOOK-KANAMORI, DENNIS - Leiden University; NORTH, KARI - University Of North Carolina; HELMINEN, MIKA - Tampere University Hospital; MOSSAVAR-RAHMANI, YASMIN - Albert Einstein College Of Medicine; SNETSELAAR, LINDA - University Of Iowa; MARTIN, LISA - George Washington University; VIIKARI, JORMA - University Of Turku; ODDY, WENDY - University Of Tasmania; PENNELL, CRAIG - University Of Newcastle; ROSENDALL, FRITS - Leiden University Medical Center; IKRAM, M. ARFAN - Erasmus Medical Center; UITTERLINDEN, ANDRE - Erasmus Medical Center; PSATY, BRUCE - University Of Washington; MOZAFFARIAN, DARIUSH - Tufts University; ROTTER, JEROME - Ucla Medical Center; TAYLOR, KENT - Ucla Medical Center; LEHTIMAKI, TERHO - University Of Tampere; RAITAKARI, OLLI - University Of Turku; LIVINGSTON, KARA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; VOORTMAN, TRUDY - Erasmus Medical Center; FOROUHI, NITA - University Of Cambridge; WAREHAM, NICHOLAS - University Of Cambridge; DE MUTSERT, RENEE - Leiden University Medical Center; RICH, STEPHEN - University Of Virginia; MANSON, JOANN - Brigham & Women'S Hospital; MORA, SAMIA - Brigham & Women'S Hospital; RIDKER, PAUL - Brigham & Women'S Hospital; MERINO, JORDI - Massachusetts General Hospital; MEIGS, JAMES - Harvard University; DASHTI, HASSAN - Massachusetts General Hospital; CHASMAN, DANIEL - Brigham & Women'S Hospital; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DUPUIS, JOSEE - Boston University School Of Public Health; HERMAN, MARK - Duke University; MCKEOWN, NICOLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Circulation: Genomic and Precision Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/21/2021
Publication Date: 7/16/2021
Citation: Haslam, D., Peloso, G.M., Guirette, M., Imamura, F., Bartz, T., Pitsillides, A., Wang, C.A., Li-Gao, R., Westra, J., Pitkanen, N., Young, K.L., Graff, M., Wood, A., Braun, K.N., Luan, J., Kahonen, M., Kiefte-de Jong, J.C., Ghanbari, M., Tintle, N., Lemaitre, R.N., Mook-Kanamori, D.O., North, K.E., Helminen, M., Mossavar-Rahmani, Y., Snetselaar, L.G., Martin, L.W., Viikari, J., Oddy, W.H., Pennell, C.E., Rosendall, F., Ikram, M., Uitterlinden, A.G., Psaty, B.M., Mozaffarian, D., Rotter, J., Taylor, K.D., Lehtimaki, T., Raitakari, O.T., Livingston, K., Voortman, T., Forouhi, N.G., Wareham, N.J., de Mutsert, R., Rich, S., Manson, J., Mora, S., Ridker, P., Merino, J., Meigs, J.B., Dashti, H.S., Chasman, D., Lichtenstein, A.H., Smith, C.E., Dupuis, J., Herman, M., McKeown, N.M. 2021. Sugar-sweetened beverage consumption may modify associations between genetic variants in the CHREBP locus and HDL-C and TG concentrations. Circulation: Genomic and Precision Medicine. https://doi.org/10.1161/CIRCGEN.120.003288.
DOI: https://doi.org/10.1161/CIRCGEN.120.003288

Interpretive Summary: Drinking sugary beverages and genetic variants near a specific gene named CHREBP have both been linked to lipid concentrations in previous studies. Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank were examined here. These data suggest that genetic variants near the CHREBP gene may change how drinking sugary beverages impacts lipid concentrations among adults.

Technical Abstract: Background - Carbohydrate responsive element binding protein (ChREBP) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. We hypothesized SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Methods - Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (N=63,599) and the UK Biobank (UKB) (N=59,220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and TG concentrations using linear regression models. A total of 1,606 single-nucleotide polymorphisms (SNPs) within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires and participants were grouped by their estimated intake. Results - In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers [beta (95% CI) = 2.12 (1.16, 3.07) mg/dl; p<0.0002], but not significantly among the lowest SSB consumers (p=0.81; pDiff<0.0001). Similar results were observed for two additional variants (rs35709627 and rs71556736). For TG, rs55673514 was positively associated with TG concentrations only among the highest SSB consumers [beta (95% CI): 0.06 (0.02, 0.09) per allele count for log(mg/dl), p=0.001], but not the lowest SSB consumers (p=0.84; pDiff=0.0005). Conclusions - Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in TG concentrations.