Association analysis of the pituitary adenylate cyclase-activating polypeptide (PACAP/ADCYAP1) gene in bipolar disorder.
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 chi contingency analysis. Linkage disequilibrium between markers was calculated and estimated haplotype frequencies were compared between groups.


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


CONCLUSIONS
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.
Lohoff
Falk W
FW
Department of Psychiatry, Translational Research Laboratory, Center for Neurobiology and Behavior, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA. lohoff@mail.med.upenn.edu
Bloch
Paul J
PJ
Weller
Andrew E
AE
Ferraro
Thomas N
TN
Berrettini
Wade H
WH
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide
C495401:ADCYAP1 protein, human; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide