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Association analysis of the pituitary adenylate cyclase-activating polypeptide (PACAP/ADCYAP1) gene in bipolar disorder

Lohoff, Falk W.; Bloch, Paul J.; Weller, Andrew E.; Ferraro, Thomas N.; Berrettini, Wade H.

doi: 10.1097/YPG.0b013e3282f60320

Background Linkage studies in bipolar disorder (BPD) suggest that a susceptibility locus exists on chromosome 18p11. The pituitary adenylate cyclase-activating polypeptide/adenylate cyclase-activating polypeptide 1 (pituitary) (PACAP/ADCYAP1) gene maps to this region. PACAP is a neuropeptide involved in neurotransmission in both the peripheral nervous system and central nervous system and is required for catecholamine secretion. Animal models of PACAP mutations show remarkable behavioral defects, including hyperactivity and increased exploratory behavior.

Objective In this study we tested the hypothesis that genetic variations in the human PACAP gene contribute to BPD.

Methods Genotyping of seven single nucleotide polymorphisms (rs1893154; rs2846811; rs8192595; rs2856966; rs928978; rs2231187; rs1610037) was performed in BPD patients (n=570) and healthy controls (n=710). Genotypes and allele frequencies were compared between groups using χ2 contingency analysis. Linkage disequilibrium between markers was calculated and estimated haplotype frequencies were compared between groups.

Main results There were no significant differences between groups on the allele, genotype or haplotype level for any of the tested single nucleotide polymorphisms.

Conclusion Our results provide no evidence of an association of the PACAP gene with BPD in this group of patients and controls. Additional studies are necessary to elucidate the BPD susceptibility locus on chromosome 18p.

Department of Psychiatry, University of Pennsylvania, Philadelphia, USA

Correspondence to Dr Falk W. Lohoff, MD, Assistant Professor of Psychiatry, Department of Psychiatry, Translational Research Laboratory, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 125 South 31st Street, Room 2213, Philadelphia, PA 19104, USA

Tel: +1 215 573 4582; fax: +1 215 573 2041; e-mail:

Received 17 December 2006 Revised 23 July 2007 Accepted 27 August 2007

© 2008 Lippincott Williams & Wilkins, Inc.