MAGI1 Copy Number Variation in Bipolar Affective Disorder and Schizophrenia

• Published in: Biological psychiatry (1969) Vol. 71; no. 10; pp. 922 - 930
• Main Authors: Karlsson, Robert, Graae, Lisette, Lekman, Magnus, Wang, Dai, Favis, Reyna, Axelsson, Tomas, Galter, Dagmar, Carmine Belin, Andrea, Paddock, Silvia
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.05.2012; Elsevier
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Bipolar affective disorder; Bipolar Disorder - genetics; Bipolar disorders; Carrier Proteins - genetics; Case-Control Studies; Cell Adhesion Molecules, Neuronal - genetics; copy number variation; DNA Copy Number Variations; Female; Genetic Predisposition to Disease; Genotype; Humans; MAGI1; MAGI2; Male; Medical sciences; Medicin och hälsovetenskap; Mood disorders; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychotic Disorders - genetics; rare variants; Schizophrenia; Schizophrenia - genetics; Sequence Deletion; MAGI1; rare variants; Bipolar affective disorder; schizophrenia; copy number variation; MAGI2; Mood disorder; Copy number; Schizophrenia; Bipolar disorder; Genetic determinism; Psychosis; Affective disorder; Genetics; Polymorphism
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2012.01.020

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.