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Biol Psychiatry. 2005 May 15;57(10):1097-102.

The breakpoint cluster region gene on chromosome 22q11 is associated with bipolar disorder.

Author information

1
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. rhashimo@ncnp.go.jp

Abstract

BACKGROUND:

Although the pathogenesis of bipolar disorder remains unclear, heritable factors have been shown to be involved. The breakpoint cluster region (BCR) gene is located on chromosome 22q11, one of the most significant susceptibility loci in bipolar disorder linkage studies. The BCR gene encodes a Rho GTPase activating protein, which is known to play important roles in neurite growth and axonal guidance.

METHODS:

We examined patients with bipolar disorder (n = 171), major depressive disorder (n = 329) and controls (n = 351) in Japanese ethnicity for genetic association using eleven single nucleotide polymorphisms (SNPs), including a missense one (A2387G; N796S), in the genomic region of BCR.

RESULTS:

Significant allelic associations with bipolar disorder were observed for three SNPs, and associations with bipolar II disorder were observed in ten SNPs including N796S SNP (bipolar disorder, p = .0054; bipolar II disorder p = .0014). There was a significant association with major depression in six SNPs. S796 allele carriers were in excess in bipolar II patients (p = .0046, odds ratio = 3.1, 95% CI 1.53-8.76). Furthermore, we found a stronger evidence for association with bipolar II disorder in a multi-marker haplotype analysis (p = .0002).

CONCLUSIONS:

Our results suggest that genetic variations in the BCR gene could confer susceptibility to bipolar disorder and major depressive disorder.

PMID:
15866548
DOI:
10.1016/j.biopsych.2005.02.019
[Indexed for MEDLINE]

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