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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #402503
Research Project: Preventing the Development of Childhood Obesity

Location: Children's Nutrition Research Center

Title: Investigating gene-diet interactions impacting the association between macronutrient intake and glycemic traits

Author
item WESTERMAN, KENNETH - Massachusetts General Hospital
item WALKER, MAURA - Boston University Medical School
item GAYNOR, SHEILA - Harvard School Of Public Health
item WESSEL, JENNIFER - Indiana University School Of Medicine
item DICORPO, DANIEL - Boston University School Of Public Health
item MA, JIANTAO - Friedman School At Tufts
item ALONSO, ALVARO - Emory University
item ASLIBEKYAN, STELLA - University Of Alabama At Birmingham
item BALDRIDGE, ABIGAIL - Northwestern University
item BERTONI, ALAIN - Wake Forest School Of Medicine
item BIGGS, MARY - University Of Washington
item BRODY, JENNIFER - University Of Washington
item CHEN, YII - Harbor-Ucla Medical Center
item DUPUIS, JOSEE - Boston University School Of Public Health
item GOODARZI, MARK - Cedars-Sinai Medical Center
item GUO, XIUQING - Harbor-Ucla Medical Center
item HASBANI, NATALIE - University Of Texas Health Science Center
item HEATH, ADAM - University Of Texas Health Science Center
item HIDALGO, BERTHA - University Of Alabama At Birmingham
item IRVIN, MARGUERITE - University Of Alabama At Birmingham
item JOHNSON, W - University Of Washington
item KALYANI, RITA - Johns Hopkins University School Of Medicine
item LANGE, LESLIE - University Of Colorado
item LEMAITRE, ROZENN - University Of Washington
item LIU, CHING - Boston University School Of Public Health
item LIU, SIMIN - Brown University
item MOON, JEE - Albert Einstein Medical Center
item NASSIR, RAMI - Non ARS Employee
item PANKOW, JAMES - University Of Minnesota
item PETTINGER, MARY - Fred Hutchinson Cancer Research Center
item RAFFIELD, LAURA - University Of North Carolina
item RASMUSSEN-TORVIK, LAURA - Northwestern University
item SELVIN, ELIZABETH - Johns Hopkins School Of Public Health
item SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC)
item SHADYAB, ALADDIN - University Of California, San Diego
item SMITH, ALBERT - University Of Michigan
item SMITH, NICHOLAS - University Of Washington
item STEFFEN, LYN - University Of Minnesota
item TALEGAKWAR, SAMEERA - George Washington University
item TAYLOR, KENT - Harbor-Ucla Medical Center
item DE VRIES, PAUL - Harbor-Ucla Medical Center
item WILSON, JAMES - Beth Israel Deaconess Medical Center
item WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item YANEK, LISA - Johns Hopkins University School Of Medicine
item YAO, JIE - Harbor-Ucla Medical Center
item ZHENG, YINAN - Northwestern University
item BOERWINKLE, ERIC - University Of Texas Health Science Center
item MORRISON, ALANNA - University Of Texas Health Science Center
item FORNAGE, MIRIAM - University Of Texas Health Science Center
item RUSSELL, TRACY - University Of Vermont College Of Medicine
item PSATY, BRUCE - University Of Washington
item LEVY, DANIEL - National Heart, Lung And Blood Institute(NHLBI, NIH)
item HEARD-COSTA, NANCY - Boston University Medical School
item RAMACHANDRAN, VASAN - Boston University Medical School
item MATHIAS, RASIKA - Johns Hopkins University School Of Medicine
item ARNETT, DONNA - University Of Kentucky
item KAPLAN, ROBERT - Stanford University School Of Medicine
item NORTH, KARI - University Of North Carolina
item CORREA, ADOLFO - University Of Mississippi Medical Center
item CARSON, APRIL - University Of Mississippi Medical Center
item ROTTER, JEROME - Harbor-Ucla Medical Center
item RICH, STEPHEN - University Of Virginia
item MANSON, JOANN - Harvard Medical School
item REINER, ALEXANDER - University Of Washington
item KOOPERBERG, CHARLES - Fred Hutchinson Cancer Research Center
item FLOREZ, JOSE - Harvard Medical School
item MEIGS, JAMES - Harvard Medical School
item MERINO, JORDI - Harvard Medical School
item TOBIAS, DEIRDRE - Brigham & Women'S Hospital
item CHEN, HAN - University Of Texas Health Science Center
item MANNING, ALISA - Massachusetts General Hospital

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2023
Publication Date: 2/15/2023
Citation: Westerman, K.E., Walker, M.E., Gaynor, S.M., Wessel, J., DiCorpo, D., Ma, J., Alonso, A., Aslibekyan, S., Baldridge, A.S., Bertoni, A.G., Biggs, M.L., Brody, J.A., Chen, Y.D., Dupuis, J., Goodarzi, M.O., Guo, X., Hasbani, N.R., Heath, A., Hidalgo, B., Irvin, M.R., Johnson, W.C., Kalyani, R.R., Lange, L., Lemaitre, R.N., Liu, C.T., Liu, S., Moon, J.Y., Nassir, R., Pankow, J.S., Pettinger, M., Raffield, L., Rasmussen-Torvik, L.J., Selvin, E., Senn, M.K., Shadyab, A.H., Smith, A.V., Smith, N.L., Steffen, L., Talegakwar, S., Taylor, K.D., de Vries, P.S., Wilson, J.G., Wood, A.C., Yanek, L.R., Yao, J., Zheng, Y., Boerwinkle, E., Morrison, A.C., Fornage, M., Russell, T.P., Psaty, B.M., Levy, D., Heard-Costa, N.L., Ramachandran, V.S., Mathias, R.A., Arnett, D.K., Kaplan, R., North, K.E., Correa, A., Carson, A., Rotter, J.I., Rich, S.S., Manson, J.E., Reiner, A.P., Kooperberg, C., Florez, J.C., Meigs, J.B., Merino, J., Tobias, D.K., Chen, H., Manning, A.K. 2023. Investigating gene-diet interactions impacting the association between macronutrient intake and glycemic traits. Diabetes. https://doi.org/10.2337/db22-0851.
DOI: https://doi.org/10.2337/db22-0851

Interpretive Summary: How much carbohydrate, fat and protein people eat, relative to each other, influences their type 2 diabetes risk (T2D). However, people react differently to their diets, and we don't understand the extent that genetic differences influence the how fat, carbohydrate and protein alter T2D risk on an individual basis. In our analyses, replacing fat with carbohydrate modestly lowered markers of T2D risk. However, when we included genetic information, we found that within one gene, at a locus enriched in people with African-American ancestry, people's genetic make-up altered this finding such that we only saw an effect of replacing carbohydrate with fat on T2D risk in people with the rarest genotype. These findings may serve as an important step in understanding how to tailor nutrition advice to people's genetic differences ("personalized nutrition") when trying to reduce the risk of T2D.

Technical Abstract: Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed N=33,187 diabetes-free participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g. for hemoglobin A1c [HbA1c], -0.013 %HbA1c per 250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that over 150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry.