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 language | English (US) |
|---|---|
| Pages (from-to) | 259-265 |
| Number of pages | 7 |
| Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
| Volume | 144 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 5 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Increase in GSK3β gene copy number variation in bipolar disorder
AU - Lachman, Herbert M.
AU - Pedrosa, Erika
AU - Petruolo, Oriana A.
AU - Coekerham, Melissa
AU - Papolos, Alexander
AU - Novak, Tomas
AU - Papolos, Demitri F.
AU - Stopkova, Pavla
PY - 2007/4/5
Y1 - 2007/4/5
N2 - 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.
AB - 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.
KW - Candidate gene
KW - Juvenile bipolar
KW - Manic depression
KW - Manic depressive illness
KW - Pediatric bipolar
UR - http://www.scopus.com/inward/record.url?scp=34247367138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247367138&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.30498
DO - 10.1002/ajmg.b.30498
M3 - Article
VL - 144
SP - 259
EP - 265
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 3
ER -