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.
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 None., Dupuis J., Dedoussis GV., Ordovas JM., Ingelsson E., Cupples LA., Siscovick DS., Franks PW., Meigs JB.
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.