Is the thrifty genotype hypothesis (TGH) supported by evidence based on confirmed type 2 diabetes (T2D) susceptibility variants?
L. Southam1, N. Soranzo2, SB. Montgomery2, K. Chapman1, MI. McCarthy1, I. Barroso2, E. Zeggini1 1) WTCHG, University of Oxford, Oxford, UK; 2) WTSI, Hinxton, UK. The TGH suggests that the high prevalence of T2D may be partly due to common genetic variants that have risen in population frequency due to natural selection having favoured alleles that were once advantageous in periods of famine. The recent detection of 18 robustly replicating T2D susceptibility loci enables us for the first time to look for evidence in support (or otherwise) of the TGH using proven loci. We have examined several characteristics that might indicate evidence for selection at the 18 loci: we have determined whether the risk allele at index single nucleotide polymorphisms (SNPs) is the derived or ancestral allele and whether the risk allele is the major or minor allele (in terms of allele frequency) in the reported studies. We find that the risk allele is the ancestral allele at 12 loci, compared to 9 expected
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