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The gene encoding the melanin-concentrating hormone receptor 1 is associated with schizophrenia in a Danish case–control sample

Demontis, Dittea; Nyegaard, Mettea,b; Christensen, Jane H.a; Severinsen, Jacoba; Hedemand, Annea; Hansen, Thomasc; Werge, Thomasc; Mors, Oled; Børglum, Anders D.a,d

doi: 10.1097/YPG.0b013e32834dc424
Original Articles

Objective The MCHR1 gene encoding the melanin-concentrating hormone receptor 1 is located on chromosome 22q13.2 and has previously been associated with schizophrenia in a study of cases and controls from the Faroe Islands and Scotland. Herein we report an association between variations in the MCHR1 gene and schizophrenia, based on analyses of a larger sample and an increased number of single nucleotide polymorphisms (SNPs) than used in the previous study.

Methods Eighteen SNPs in the MCHR1 gene region were genotyped in a Caucasian case–control sample from Denmark consisting of 390 individuals with schizophrenia and 814 control individuals. Sex-specific analysis and analysis of association with antipsychotic treatment were performed.

Results Five SNPs in the proximal region of MCHR1 were significantly associated with schizophrenia. The associations seemed to be sex specific, predominantly seen in men where one SNP (rs133073) remained significant (P=0.003) after correction for multiple testing. When combining the P values in the proximal region of MCHR1, the region-wise P value was low (P=0.009) supporting that variations in this part of the gene is associated with schizophrenia. Furthermore, the association was stronger in patients responding to conventional and atypical antipsychotic medication except clozapine.

Conclusion Our results suggest that MCHR1 may influence schizophrenia susceptibility, in particular among men and patients responding to conventional (nonclozapine) treatment.

aDepartment of Human Genetics, Aarhus University, Århus C

bDepartment of Haematology, Aalborg Hospital Science and Innovation Center, Aarhus University Hospital, Aalborg

cResearch Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde

dCentre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

Correspondence to Ditte Demontis, PhD, Department of Human Genetics, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Århus C, Denmark Tel: +45 89421935; fax: +45 8612 3173; e-mail:

Received February 27, 2011

Accepted August 15, 2011

© 2012 Lippincott Williams & Wilkins, Inc.