The association of the HOPA(12bp) polymorphism with schizophrenia in the NIMH Genetics Initiative for Schizophrenia sample.

HOPA (MED12) is an X-chromosome gene that codes for a critical member of the Mediator Complex, a group of proteins that regulates transcription via the nuclear receptor, Wnt and Receptor Tyrosine Kinase pathways. In prior association and meta-analyses, we have shown that the presence of an evolutionarily conserved, 12 bp (4 amino acid) insertional polymorphism in exon 43 of this gene is associated with increased risk for an endophenotype of schizophrenia. In this communication, we describe the results of our work with subjects and data from the National Institutes of Mental Health (NIMH) Genetics Initiative for Schizophrenia. We report that the presence of the HOPA(12bp) polymorphism is associated with increased risk for schizophrenia in subjects of European ancestry. In the light of this new study and the prior wealth of clinical and basic science data, we conclude that the HOPA(12bp) allele is a risk factor for schizophrenia in subjects of European ancestry and suggest that further studies to define the endophenotype and mechanisms of illness associated with this polymorphism are indicated.