An association study of the neuregulin 1 gene, bipolar affective disorder and psychosis.

Abstract

OBJECTIVE:

As evidence of partial aetiological overlap between bipolar affective disorder and schizophrenia is accumulating, it is important to determine whether genes implicated in the aetiology of schizophrenia play a role in bipolar disorder, and vice versa. As the neuregulin 1 (NRG1) gene has been associated with schizophrenia, we set out to investigate whether it is also associated with bipolar affective disorder, using a sample from Scotland, UK.

METHODS:

We tested four single nucleotide polymorphisms (SNPs), SNP8NRG221533 (rs35753505), SNP8NRG241930, SNP8NRG243177 (rs6994992) and SNPNRG222662 (rs4623364) for allelic and haplotypic association with bipolar disorder and the presence of psychotic or mood-incongruent psychotic features.

RESULTS:

We found nominal allele-wise significant association (P = 0.02) for SNP8NRG221533, with the T allele being overrepresented in cases. This is the opposite allelic association to the original association study where the C allele was associated with schizophrenia. Allele-wise significance increased when we tested for association with the subgroups of bipolar disorder with psychotic features (chi2 = 8.53; P = 0.003; odds ratio = 1.49) and, more specifically, with mood-incongruent psychotic features (chi2 = 7.13; P = 0.008; odds ratio = 1.57). Furthermore, both these subphenotypes were significantly associated with the SNP8NRG221533(T)-SNP8NRG241930(G) haplotype (chi2 = 11.94, global P = 0.027 and chi2 = 11.88, global P = 0.019, respectively) and with the SNP8NRG221533(T)-SNP8NRG222662(C)-SNP8NRG241930(G) haplotype (chi2 = 19.98, global P = 0.009) in case of the broader subphenotype of psychotic bipolar.

CONCLUSION:

This study supports the hypothesis that NRG1 may play a role in the development of bipolar disorder, especially in psychotic subtypes, albeit with different alleles to previous association reports in schizophrenia and bipolar disorder.

• Authors: Diana P Prata, Gerome Breen, Sarah Osborne, Janet Munro, David St Clair, David A Collier
• Journal: Psychiatric genetics (Psychiatr Genet) Vol. 19 Issue 3 Pg. 113-6 (Jun 2009) ISSN: 1473-5873 [Electronic] England
• PMID: 19339916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NRG1 protein, human
• Nerve Tissue Proteins
• Neuregulin-1

Topics

• Alleles
• Bipolar Disorder (genetics)
• Genome-Wide Association Study
• Humans
• Nerve Tissue Proteins (genetics)
• Neuregulin-1
• Polymorphism, Single Nucleotide
• Psychotic Disorders (genetics)
• Scotland