title: Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression.
abstract: Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Delacrétaz
authors.affiliation: Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Preisig
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Frederik
authors.initials: F
authors.lastname: Vandenberghe
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Nuria
authors.initials: N
authors.lastname: Saigi Morgui
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Lina
authors.initials: L
authors.lastname: Quteineh
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Choong
authors.affiliation: Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gholam-Rezaee
authors.affiliation: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kutalik
authors.affiliation: Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland; Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Magistretti
authors.affiliation: Division of Psychiatric Specialties, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Aubry
authors.affiliation: Service of Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Armin
authors.initials: A
authors.lastname: von Gunten
authors.affiliation: Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Enrique
authors.initials: E
authors.lastname: Castelao
authors.affiliation: Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.affiliation: Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Waeber
authors.affiliation: Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003863:Depression / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011979:Receptors, Pituitary Hormone / Q000235:genetics*; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics
chemical_list: C431280:MCHR2 protein, human; C000608144:MCHR2-AS1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone