All three of these signals are detected here with effect-sizes consistent with previous reports (Table 2). A cluster of SNPs on chromosome 10q, within TCFL2, represented by rs4506565 (trend test, OR 1.36, P=5.7×10-13) generates the strongest association signal for T2D (Table 3, Fig. 5). Rs4506565 is in tight linkage disequilibrium (r2 of 0.92 in the CEU component of HapMap) with rs7903146, the variant with the strongest aetiological claims104,106. In fact, our imputation analysis confirms that rs7903146, though unrepresented on the chip, is responsible for the strongest association effect in this region (Fig. 5). TCF7L2 acts within the WNT-signalling pathway, and effects on diabetes risk seem to be mediated predominantly through beta-cell dysfunction107.
