Increase in GSK3β gene copy number variation in bipolar disorder

Herbert M. Lachman, Erika Pedrosa, Oriana A. Petruolo, Melissa Coekerham, Alexander Papolos, Tomas Novak, Demitri F. Papolos, Pavla Stopkova

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The analysis of submicroscopic copy number variations (CNVs), also known as copy number polymorphisms (CNPs), is emerging as a new tool for understanding the genetic basis of cancer, developmental disorders, and complex traits. One area where this may be particularly useful is in the identification of genetic variants underlying schizophrenia (SZ) and bipolar disorder (BD). Linkage analysis and pharmacological studies carried out over the past decade have implicated a number of positional and physiological candidate genes. Yet, despite extensive analysis, the underlying allelic variants responsible for disease susceptibility have remained, largely, elusive. Although the borders of most CNV have not been precisely mapped, it appears that a considerable number of SZ and BD candidate genes have their coding elements disrupted by polymorphic CNVs, suggesting that these would be good variants to consider for underlying disease susceptibility. One such gene is GSK3β, which codes for glycogen synthase kinase, a key component of the Wnt signaling pathway and a target of lithium salts. A CNV in the GSK3β locus at chromosome 3q13.3 appears to disrupt the gene's 3′-coding elements. The CNV also affects two other annotated, genes. We now report that patients with BD have an increased frequency of this CNV - primarily the duplication variant - compared with controls (P = 0.002). The finding suggests that GSK3β may be involved in BD susceptibility in some individuals and that CNVs in this and other candidate genes for psychiatric disorders should be analyzed as causative functional genetic variants.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume144
Issue number3
DOIs
StatePublished - Apr 5 2007

Fingerprint

Gene Dosage
Bipolar Disorder
Genes
Disease Susceptibility
Schizophrenia
DNA Copy Number Variations
Glycogen Synthase Kinases
Wnt Signaling Pathway
Lithium
Psychiatry
Salts
Chromosomes
Pharmacology
Neoplasms

Keywords

  • Candidate gene
  • Juvenile bipolar
  • Manic depression
  • Manic depressive illness
  • Pediatric bipolar

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Increase in GSK3β gene copy number variation in bipolar disorder. / Lachman, Herbert M.; Pedrosa, Erika; Petruolo, Oriana A.; Coekerham, Melissa; Papolos, Alexander; Novak, Tomas; Papolos, Demitri F.; Stopkova, Pavla.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 144, No. 3, 05.04.2007, p. 259-265.

Research output: Contribution to journalArticle

Lachman, HM, Pedrosa, E, Petruolo, OA, Coekerham, M, Papolos, A, Novak, T, Papolos, DF & Stopkova, P 2007, 'Increase in GSK3β gene copy number variation in bipolar disorder', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 144, no. 3, pp. 259-265. https://doi.org/10.1002/ajmg.b.30498
Lachman, Herbert M. ; Pedrosa, Erika ; Petruolo, Oriana A. ; Coekerham, Melissa ; Papolos, Alexander ; Novak, Tomas ; Papolos, Demitri F. ; Stopkova, Pavla. / Increase in GSK3β gene copy number variation in bipolar disorder. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2007 ; Vol. 144, No. 3. pp. 259-265.
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