MEGF10 association with schizophrenia

Background: The 5q21-31 region has been implicated as harboring risk genes for schizophrenia in many linkage studies. In our previous report of stepwise fine mapping of this region, the MEGF10 gene was one of the genes showing consistent associations in our screening subsample. In this study, we carried out independent replication and expression studies of the MEGF10 gene. Methods: Association studies with 8 SNPs in the MEGF10 gene were performed in the Irish case-control study of schizophrenia (ICCSS) sample (652 case and 617 control subjects). The expression of MEGF10 was also compared between healthy control subjects and schizophrenia patients using postmortem brain cDNA libraries. Results: In the ICCSS sample, associations with the disease were found in the same risk alleles and haplotypes as that observed in our fine-mapping studies. The major allele (A) of rs27388 was overrepresented in affected individuals (p =.0169), which remained significant after correction for multiple testing. In expression studies, MEGF10 had higher expression levels in the affected than the unaffected (P =.015). Schizophrenia patients with a 1/1 genotype at rs27388 had higher expressions than those patients with 1/2 and 2/2 genotypes (p =.0008). Conclusions: Evidence from both association and expression studies suggests that MEGF10 is likely associated with schizophrenia. The major allele and 1/1 genotype at rs27388 impose higher risks for the disease.