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Background  TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in  TCF7L2  have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence.    Results  We included 26,905 individuals without diabetes from the Malmö Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including  TCF7L2  (rs7903146 and rs12255372),  HHEX  (rs1111875),  HNF1A  (rs7957197),  NOTCH2  (rs10923931),  TLE4  (rs13292136),  ZBED3  (rs4457053), and  PPARG  (rs1801282 and rs13081389). SNPs in  TCF7L2 ,  NOTCH2 , and  ZBED3  showed significant interactions with fiber intake on type 2 diabetes incidence ( P  interaction  = 0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the  TCF7L2  risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the  NOTCH2  variant and homozygotes of the risk allele of the  ZBED3  variant.    Conclusions  Our results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence.    Electronic supplementary material  The online version of this article (doi:10.1186/s12263-016-0524-4) contains supplementary material, which is available to authorized users.

genes and nutrition

Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes