Authors' reply

Dr Ohi is correct that the risk allele at the locus rs7914558 is the major G allele; throughout the paper we had incorrectly identified the risk allele as being the major A allele. ¹ We have submitted a corrigendum to state that the G allele is both the major allele and the risk allele.

However, while the tables and text have incorrectly named the risk allele as the A allele, the analysis undertaken, and its interpretation, are correct, as we based our analysis on the major allele being the risk allele. As we state in our study, the risk allele was associated with reduced self-serving bias, and increased grey matter volume in regions relevant to social cognition in both the Irish and Italian samples. Dr Ohi, therefore, seems to be incorrect in asserting that the results are consistent with data from his group’s study, in which the risk allele was associated with reduced grey matter volume in the orbitofrontal cortex. Although both regions are associated with social cognition, they are also implicated in other cognitive processes, which might explain the differences in results. While both sets of results will require replication in independent samples before firm conclusions are drawn, the availability of a replication sample in our study enabled us to provide additional support for our results, despite their counterintuitive nature.

We also take this opportunity to disagree with Dr Ohi’s assertion that this variant rs7914558 is necessarily associated with CNNM2. Although the title of our paper notes that this variant is located at the same locus as CNNM2, and named as such in the PGC GWAS study, we highlight in our discussion that linkage disequilibrium from this variant extends to three other genes over a region of several hundred kb, any one of which could potentially be associated with this signal. In fact, the most recent study by the PGC ² suggests, based on eQTL analysis, that the single-nucleotide polymorphism most strongly associated with schizophrenia in this region (rs11191419) is associated with altered expression of the AS3MT gene.