Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts

Jennifer A. Nettleton, Marie France Hivert, Rozenn N. Lemaitre, Nicola M. McKeown, Dariush Mozaffarian, Toshiko Tanaka, Mary K. Wojczynski, Adela Hruby, Luc Djoussé, Julius S. Ngwa, Jack L. Follis, Maria Dimitriou, Andrea Ganna, Denise K. Houston, Stavroula Kanoni, Vera Mikkilä, Ani Manichaikul, Ioanna Ntalla, Frida Renström, Emily SonestedtFrank J A Van Rooij, Stefania Bandinelli, Lawrence De Koning, Ulrika Ericson, Neelam Hassanali, Jessica C. Kiefte-De Jong, Kurt K. Lohman, Olli Raitakari, Constantina Papoutsakis, Per Sjogren, Kathleen Stirrups, Erika Ax, Panos Deloukas, Christopher J. Groves, Paul F. Jacques, Ingegerd Johansson, Yongmei Liu, Mark I. McCarthy, Kari North, Jorma Viikari, M. Carola Zillikens, Josée Dupuis, Albert Hofman, Genovefa Kolovou, Kenneth Mukamal, Inga Prokopenko, Olov Rolandsson, Ilkka Seppälä, L. Adrienne Cupples, Frank B. Hu, Mika Kähönen, André G. Uitterlinden, Ingrid B. Borecki, Luigi Ferrucci, David R. Jacobs, Stephen B. Kritchevsky, Marju Orho-Melander, James S. Pankow, Terho Lehtimäki, Jacqueline C M Witteman, Erik Ingelsson, David S. Siscovick, George Dedoussis, James B. Meigs, Paul W. Franks

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70 Scopus citations


Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG (β =-0.004 mmol/L, 95% confidence interval:-0.005,-0.003) and FI (β =-0.008 ln-pmol/L, 95% confidence interval:-0.009,-0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG-and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalAmerican journal of epidemiology
Issue number2
StatePublished - Jan 2013


  • diabetes
  • dietary pattern
  • gene-environment interaction
  • glucose
  • insulin


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