The breakpoint cluster region gene on chromosome 22q11 is associated with bipolar disorder.
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.
Hashimoto
Ryota
R
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. rhashimo@ncnp.go.jp
Okada
Takeya
T
Kato
Tadafumi
T
Kosuga
Asako
A
Tatsumi
Masahiko
M
Kamijima
Kunitoshi
K
Kunugi
Hiroshi
H
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D017931:DNA Primers; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D017931:DNA Primers