Bipolar disorder (BPD) and schizophrenia (SZ) are common, sever psychiatric syndromes which are partially heritable. Five linkage studies have identified 18p11.2 as a candidate region, which contains a susceptibility gene for BPD and/or SZ. One of the groups reporting linkage also reports strong (p=0.00009) linkage disequilibrium (LD) between SZ and an 18p11.2 (CA)n repeat polymorphism, located in intron 5 of a G-protein subunit gene, GOLF. We have discovered a novel 18p11.2 candidate susceptibility gene in GOLF intron 5. This novel gene, which contains the GOLF (CA)n repeat in its 3'TTR, encodes a brain-specific secreted neuropeptide. This novel gene has no homology to any gene n the public databases. It is an intronless gene with a 116 amino acid open reading frame, including a signal peptide. In situ hybridization and immunohistochemistry reveal that expression is limited to the hippocampus, amygdala and entorhinal cortex. No peripheral expression has been detected. A case-control association study of transcribed variants yields evidence for association with SZ. These data suggest that this novel candidate gene deserves further study. Support is requested for family-based LD studies of these (and other) variants in both BPD and SZ. We have assembled sets (n>600) of parent-child trios for both SZ and BPD to test the hypothesis that variation in this gene increases risks for these disorders. These studies may identify a susceptibility gene for SZ and/or BPD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063876-03
Application #
6765161
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Lehner, Thomas
Project Start
2002-06-01
Project End
2005-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
3
Fiscal Year
2004
Total Cost
$158,500
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lohoff, Falk W; Weller, Andrew E; Bloch, Paul J et al. (2008) Association between the catechol-O-methyltransferase Val158Met polymorphism and cocaine dependence. Neuropsychopharmacology 33:3078-84
Lohoff, Falk W; Bloch, Paul J; Weller, Andrew E et al. (2008) Genetic variants in the cocaine- and amphetamine-regulated transcript gene (CARTPT) and cocaine dependence. Neurosci Lett 440:280-3
Lohoff, Falk W; Bloch, Paul J; Weller, Andrew E et al. (2008) Association analysis of the pituitary adenylate cyclase-activating polypeptide (PACAP/ADCYAP1) gene in bipolar disorder. Psychiatr Genet 18:53-8
Lohoff, Falk W; Weller, Andrew E; Bloch, Paul J et al. (2008) Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (VAPA) gene on chromosome 18p and bipolar disorder. J Neural Transm 115:1339-45
Lohoff, Falk W; Weller, Andrew E; Bloch, Paul J et al. (2008) Association between polymorphisms in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) on chromosome 8p and schizophrenia. Neuropsychobiology 57:55-60
Weller, Andrew E; Dahl, John P; Lohoff, Falk W et al. (2006) Analysis of variations in the NAPG gene on chromosome 18p11 in bipolar disorder. Psychiatr Genet 16:3-8
Lohoff, Falk W; Dahl, John P; Ferraro, Thomas N et al. (2006) Variations in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) are associated with bipolar i disorder. Neuropsychopharmacology 31:2739-47
McNabb, Leilah D; Moore, Katharine W; Scena, Jaqueline E et al. (2005) Association analysis of CHMP1.5 genetic variation and bipolar disorder. Psychiatr Genet 15:211-4
Lohoff, Falk W; Ferraro, Thomas N; McNabb, Leilah et al. (2005) No association between common variations in the neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) and bipolar I disorder. Psychiatry Res 135:171-7
Lohoff, Falk W; Berrettini, Wade H (2005) Lack of association between variations in the melanocortin 5 receptor gene and bipolar disorder. Psychiatr Genet 15:255-8

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