The TCF7L2 diabetes risk variant is associated with HbA₁(C) levels: a genome-wide association meta-analysis

Christopher S Franklin, Yurii S Aulchenko, Jennifer E Huffman, Veronique Vitart, Caroline Hayward, Ozren Polašek, Sara Knott, Lina Zgaga, Tatijana Zemunik, Igor Rudan, Harry Campbell, Alan F Wright, Sarah H Wild, James F Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Genome-wide association (GWA) studies have identified around 20 common genetic variants influencing the risk of type 2 diabetes (T2D). Likewise, a number of variants have been associated with diabetes-related quantitative glycaemic traits, but to date the overlap between these genes and variants has been low. The majority of genetic studies have focused on fasting plasma glucose levels; however, this measure is highly variable. We have conducted a GWA meta-analysis of glycated haemoglobin (HbA₁(C) ) levels within three healthy nondiabetic populations. This phenotype provides an estimate of mean glucose levels over 2-3 months and is a more stable predictor of future diabetes risk. Participants were from three isolated populations: the Orkney Isles in the north of Scotland, the Dalmatian islands of Vis, and Korčula in Croatia (total of 1782 nondiabetic subjects). Association was tested in each population and results combined by meta-analysis. The strongest association was with the TCF7L2 gene (rs7903146, P= 1.48 × 10⁻⁷). This is also the strongest common genetic risk factor for T2D but it has not been identified in previous genome-wide studies of glycated haemoglobin.
Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalAnnals of human genetics
Volume74
Issue number6
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Croatia
  • Diabetes Mellitus, Type 2
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Hemoglobin A, Glycosylated
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Scotland
  • Transcription Factor 7-Like 2 Protein
  • Young Adult

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