It is interesting to compare the effect of ENIGMA’s top SNPs with the effects of common psychiatric and neurological conditions on hippocampal volumes. In a recent meta-analysis (Barnes et al., 2009), patients with Alzheimer’s disease have a 24.1 % mean hippocampal volume deficit. Patients with mild cognitive impairment have a 15.3 % deficit relative to cognitively healthy controls (calculated from Table 9 in Leung et al. 2010). In psychiatric disorders, the hippocampal volume deficit is typically reported to be smaller. Although hippocampal volume deficits are one of the more robust MRI findings in schizophrenia, they are not always evident in single site studies (Shenton et al. 2001). The ENIGMA Disease Working Groups now suggest a mean hippocampal volume deficit, relative to controls, of around 3.6 % in schizophrenia and 2.9 % in bipolar disorder—depending, of course, on cohort-specific factors (medication, duration of illness, etc.). By contrast, in ENIGMA1, the rs7294919 genetic variant was associated with a hippocampal volume decreased by 47.6 mm3 or by 1.2 % of the average hippocampal volume per risk allele. Bearing in mind that the cause
