title: Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression.
abstract: Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD.
  
  
  
  The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored.
  
  
  
  CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=-0.75kg/m(2), 95% CI -1.30 to -0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study.
  
  
  
  Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample.
  
  
  
  CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases.
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: 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: Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Spain; MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
authors.forename: Margarita
authors.initials: M
authors.lastname: Rivera
authors.affiliation: Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
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: 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: 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: Aurélie
authors.initials: A
authors.lastname: Delacrétaz
authors.affiliation: Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland; Child and Adolescent Psychiatric Clinic, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Cardinaux
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ching-López
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. Electronic address: chin.eap@chuv.ch.
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D000273:Adipose Tissue; D000328:Adult; D015415:Biomarkers; D015992:Body Mass Index; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000150:complications* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; C500984:CRTC1 protein, human; D014157:Transcription Factors
keywords: Genetic polymorphisms; Major depressive disorder; Obesity; Pharmacogenetics; Psychiatric disorders; Psychotropic drugs