Background
Bipolar affective disorder (BPAD) and schizophrenia (SZ) are devastating psychiatric
disorders that each affect about 1% of the population worldwide. Identification of
new drug targets is an important step toward better treatment of these poorly understood
diseases.
Methods
Genome-wide copy number variation (CNV) was assessed and variants were ranked by co-occurrence
with disease in 48 BPAD families. Additional support for involvement of the highest-ranking
CNV from the family-based analysis in psychiatric disease was obtained through analysis
of 4084 samples with BPAD, SZ, or schizoaffective disorder. Finally, a pooled analysis
of in-house and published datasets was carried out including 10,925 cases with BPAD,
SZ, or schizoaffective disorder and 16,747 controls.
Results
In the family-based analysis, an approximately 200 kilobase (kb) deletion in the first
intron of the MAGI1 gene was identified that segregated with BPAD in a pedigree (six out of six affected
individuals; parametric logarithm of the odds score = 1.14). In the pooled analysis,
seven additional insertions or deletions over 100 kb were identified in MAGI1 in cases, while only two such CNV events were identified in the same gene in controls
(p = .023; Fisher's exact test). Because earlier work had identified a CNV in the close
relative MAGI2 in SZ, the study was extended to include MAGI2. In the pooled analysis of MAGI2, two large deletions were found in cases, and two
duplications were detected in controls.
Conclusions
Results presented herein provide further evidence for a role of MAGI1 and MAGI2 in BPAD and SZ etiology.
Key Words
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Article info
Publication history
Published online: March 01, 2012
Accepted:
January 12,
2012
Received in revised form:
January 11,
2012
Received:
March 1,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
