Serotonin is elevated in risk-genotype carriers of TCF7L2 - rs7903146

Sci Rep. 2019 Sep 6;9(1):12863. doi: 10.1038/s41598-019-49347-y.


The transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146 is known to be tightly associated with an elevated risk for type 2 diabetes, whereas the molecular mechanisms remain elusive. We evaluated the metabolic profile of a total of 394 patients' serum samples with respect to their rs7903146 genotype using targeted metabolomics in a discovery (n = 154) and a validation (n = 240) study. We have identified serotonin as the top metabolite being increased in carriers of the risk allele. Serotonin was significantly associated with the rs7903146 genotype after full adjustment including type 2 diabetes and further top ranked metabolites. Given the role of peripheral serotonin in metabolic homeostasis and type 2 diabetes, this finding provides a first hint that the well-known impact of the TCF7L2 polymorphism on type 2 diabetes risk may involve a serotonin-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / statistics & numerical data
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Metabolomics / methods
  • Metabolomics / statistics & numerical data
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Serotonin / blood*
  • Transcription Factor 7-Like 2 Protein / genetics*


  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Serotonin