Association study between the Down syndrome cell adhesion molecule (DSCAM) gene and bipolar disorder.
OBJECTIVE
Defects of neurodevelopmental processes are suggested to underlie the pathogenesis of bipolar disorder. Down syndrome cell adhesion molecule (DSCAM), a member of neural immunoglobulin superfamily playing a diverse role for neural development, is mapped to chromosome 21q22, a linkage locus for bipolar disorder, and is, therefore, an interesting candidate for the disease.


METHODS
We performed a variation screening of the gene and association studies in 22 multiplex bipolar pedigrees of Caucasian descent and 119 Japanese patients with bipolar disorder and 140 controls. Expression levels of DSCAM were also examined in postmortem brains from the Stanley Medical Research Institute.


RESULTS
We found 27 single nucleotide polymorphisms in DSCAM. Possible associations of SNP DC141 (IVS27-15A>G; P=0.042) and DC142 (IVS29+328C>A; P=0.036) were observed in pedigree samples, and G allele of DC141 was correlated with increased expression levels of DSCAM (P=0.038) in postmortem brains. Possible association of DC136 (4749C>T), which is in the same haplotype block with DC141 and DC142, was detected in Japanese populations (P=0.049).


CONCLUSIONS
These results suggest the possible contribution of DSCAM gene in bipolar disorder, and warrant further investigations.
Amano
Kenji
K
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Japan.
Yamada
Kazuo
K
Iwayama
Yoshimi
Y
Detera-Wadleigh
Sevilla D
SD
Hattori
Eiji
E
Toyota
Tomoko
T
Tokunaga
Katsushi
K
Yoshikawa
Takeo
T
Yamakawa
Kazuhiro
K
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics
D015815:Cell Adhesion Molecules; C110833:DSCAM protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger