Study replicates BRD1 gene link to schizophrenia, BD susceptibility

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10 March 2010

MedWire News: The bromo-domain containing protein 1 (BRD1) gene is implicated in the susceptibility to schizophrenia (SZ) and bipolar disorder (BD), confirm findings of an association study.

“A recent study published by our group implicated the BRD1 gene located at chromosome 22q13.33 with schizophrenia and BD susceptibility and provided evidence suggesting a possible role for BRD1 in neurodevelopment,” explain Anders Børglum (Aarhus University, Denmark) and colleagues.

The current study findings therefore replicate the previously found associations and add further support for the involvement of BRD1 in SZ and BD susceptibility.

For the study, the researchers analyzed two overlapping case-control samples. The UK/Denmark (DK) sample included 490 patients with BD, 527 patients with SZ, and 601 healthy controls with no history of psychiatric illness. The English BD cases and controls included in the UK/DK sample were a subsample of the University College London (UCL) bipolar sample comprising 506 BD cases and 510 controls.

The single nucleotide polymorphisms (SNPs) selected for genotyping in the UK/DK sample were seven BRD1 SNPs and four SNPs in the neighboring zinc finger, BED-type containing 4 (ZBED4) gene, a brain-expressed gene of unknown function. For the UCL sample, genotypes from all SNPs within the BRD1 and ZBED4 genes were analyzed.

The researchers found significant marker associations with SZ for six BRD1/ZBED4 SNPs in the UK/DK sample. Furthermore, two SNPs in BRD1, rs4468 and rs138880, that were previously found to be associated with SZ were replicated in this study, with the minor allele over-represented among patients with SZ in both samples.

However, the association of SZ and BD with the specific two-marker risk haplotype identified in the previous Scottish study sample was not replicated, suggesting “the presence of different underlying susceptibility variants in the Scottish and the UK/DK populations,” say the researchers.

No association with BD was found in the UK/DK sample. However, analysis of data on seven BRD1 SNPs obtained from a parallel BD genome-wide association study of the UCL BD sample identified significant single-marker associations with BD for all SNPs in BRD1.

“Our data suggest that BRD1 might be a shared risk gene for BD and schizophrenia,” write the authors in the American Journal of Medical Genetics.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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