Hemani et al. reply

Replying to A. R. Wood et al. , 10.1038/nature13691 (2014). We thank Wood 1 for their interesting observations and although their proposed mechanism does not explain all our reported results, we acknowledge that alternative mechanisms could be behind the observation of epistatic signals. Although we replicate our results in large, independent samples, 19/30 of our reported interactions (Table 1 in ref. 2), Wood et al.1 do not replicate in the InCHIANTI data set (n = 450) at a type-I error rate of 0.05/30 = 0.002, including none of our reported cis–trans interactions. Having insufficient data to replicate the discovery interactions makes it problematic to draw firm conclusions on the reported cis–trans effects.