Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.
OBJECTIVE: Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS: Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. RESULTS: Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS: Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.
Nettleton, JA; McKeown, NM; Kanoni, S; Lemaitre, RN; Hivert, M-F; Ngwa, J; van Rooij, FJA; Sonestedt, E; Wojczynski, MK; Ye, Z; Tanaka, T; Garcia, M; Anderson, JS; Follis, JL; Djousse, L; Mukamal, K; Papoutsakis, C; Mozaffarian, D; Zillikens, MC; Bandinelli, S; Bennett, AJ; Borecki, IB; Feitosa, MF; Ferrucci, L; Forouhi, NG; Groves, CJ; Hallmans, G; Harris, T; Hofman, A; Houston, DK; Hu, FB; Johansson, I; Kritchevsky, SB; Langenberg, C; Launer, L; Liu, Y; Loos, RJ; Nalls, M; Orho-Melander, M; Renstrom, F; Rice, K; Riserus, U; Rolandsson, O; Rotter, JI; Saylor, G; Sijbrands, EJG; Sjogren, P; Smith, A; Steingrímsdóttir, L; Uitterlinden, AG; Wareham, NJ; Prokopenko, I; Pankow, JS; van Duijn, CM; Florez, JC; Witteman, JCM; MAGIC Investigators, ; Dupuis, J; Dedoussis, GV; Ordovas, JM; Ingelsson, E; Cupples, LA; Siscovick, DS; Franks, PW; Meigs, JB
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