Although the association with rs7341475 did not meet criteria for genome-wide significance (i.e., corrected for multiple testing), the supportive data from four replication samples and the biological plausibility of the involvement of RELN in brain abnormalities73 make these results particularly intriguing. However, mechanistic studies demonstrating functionality of the associated intronic SNP, or a SNP in LD with rs7341475, are still needed. Interestingly, however, higher expression of the RELN gene (in layer I neurons) in women compared to men and a reduction of RELN expression (in the superficial interstitial white matter neurons) in men with schizophrenia but not in females with schizophrenia74, suggests sex-specific gene regulation. Whether the schizophrenia-associated variation is also associated RELN expression differences in women remains to be determined.
