Being able to determine parental origin of alleles and haplotypes in large samples opens up new avenues to study associations between sequence variants and human traits. Standard association analysis provides suboptimal power to discover disease susceptibility variants that exhibit parental-origin specific effects. Even when association can be established, the true effect is underestimated. Rs2334499 did not capture serious attention even with the large collaborative effort of the DIAGRAM consortium. However, its contribution to T2D, measured by the recurrent risks of siblings generated, is second only to that of the TCF7L2 variant among the known susceptibility variants (Supplementary Information and Supplementary Figure 2). Sequence variants such as rs2334499 that can confer both risk and protection depending on parental origin can lead to balanced selection and in that promote diversity.
