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Epistatic interaction between CRHR1 and AVPR1b variants as a predictor of major depressive disorder

Szczepankiewicz, Aleksandraa,c; Leszczyńska-Rodziewicz, Annaa,b; Pawlak, Joannaa,b; Rajewska-Rager, Aleksandrab; Wilkosc, Monikad; Zaremba, Dorotaa; Dmitrzak-Weglarz, Monikaa; Skibinska, Mariaa; Hauser, Joannaa,b

doi: 10.1097/YPG.0000000000000007
Original Articles

Objective Genes involved in the regulation of the hypothalamus–pituitary–adrenal axis are responsible for altered susceptibility to mood disorders. The aim of this study was to analyze the possible association of CRHR1 and AVPR1b gene variants with bipolar disorder and major depressive disorder (MDD).

Methods In the study, we included 486 patients with bipolar disorder and 215 patients with MDD. Consensus diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria, using the Structured Clinical Interview for DSM Disorders. The control group consisted of 712 healthy participants. Genotyping of CRHR1 and AVPR1b polymorphisms was performed using TaqMan single nucleotide polymorphism genotyping assays. Linkage disequilibrium analysis was carried out on Haploview. Gene–gene interactions were analyzed using the multifactor dimensionality reduction method.

Results By single marker analysis we have found an association of rs28536160 of AVPR1b and rs4076452 and rs16940655 of CRHR1 with mood disorders (P=0.036, 0.0013, and 0.003, respectively). We observed strong linkage disequilibrium between seven CRHR1 polymorphisms grouped in two haplotype blocks; however, none of them showed an association with MDD or bipolar disorder. Similarly, no association was found for three of four strongly linked AVPR1b polymorphisms. Gene–gene interaction analysis revealed a significant epistatic interaction between AVPR1b and CRHR1 genes in susceptibility to MDD (P=0.017).

Conclusion Polymorphisms of CRHR1 and AVPR1b may modify susceptibility to mood disorders.

aDepartment of Psychiatry, Laboratory of Psychiatric Genetics

bDepartment of Adult Psychiatry

cDepartment of Pulmonology, Pediatric Allergy, and Clinical Immunology, Laboratory of Molecular and Cell Biology, Poznan University of Medical Sciences, Poznan

dDepartment of Individual Differences Psychology, Psychology Institute, Kazimierz Wielki University in Bydgoszcz, Bydgoszcz, Poland

Correspondence to Aleksandra Szczepankiewicz, PhD, Department of Pediatric Pulmonology, Allergy, and Clinical Immunology, Laboratory of Molecular and Cell Biology, Poznan University of Medical Sciences, 27/33 Szpitalna St., 60-572 Poznan, Poland Tel: +48 061 8491311; fax: +48 061 8480111; e-mail:

Received March 23, 2012

Accepted March 4, 2013

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins