title: 16p11.2 Locus modulates response to satiety before the onset of obesity.
abstract: The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown.
  
  
  
  This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs.
  
  
  
  We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia.
  
  
  
  Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI.
  
  
  
  These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: A M
authors.initials: AM
authors.lastname: Maillard
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Hippolyte
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.|LREN-Département des Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Rodriguez-Herreros
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: S J R A
authors.initials: SJ
authors.lastname: Chawner
authors.affiliation: Department of Psychology, Clinical Psychology and Psychotherapy, University of Fribourg, Fribourg, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Dremmel
authors.affiliation: CIBER Fisiopatologia Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Barcelona, Spain.|Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.
authors.forename: Z
authors.initials: Z
authors.lastname: Agüera
authors.affiliation: CIBER Fisiopatologia Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Barcelona, Spain.|Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.
authors.forename: A B
authors.initials: AB
authors.lastname: Fagundo
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Pain
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.|LREN-Département des Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Martin-Brevet
authors.affiliation: Integrated Research and Treatment Center Adiposity Diseases, Department of Medical Psychology and Medical SocCiology, University of Leipzig Medical Center, Leipzig, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hilbert
authors.affiliation: Department of Psychology, Clinical Psychology and Psychotherapy, University of Fribourg, Fribourg, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Kurz
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Etienne
authors.affiliation: LREN-Département des Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.|Department of Neurology, Max-Planck Institute for Human Cognitive and Brain Science, Leipzig, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Draganski
authors.affiliation: CIBER Fisiopatologia Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Barcelona, Spain.|Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.|Clinical Sciences Department, School of Medicine, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Jimenez-Murcia
authors.affiliation: Estonian Genome Center, Tartu University Hospital, Tartu, Estonia.|Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Männik
authors.affiliation: Estonian Genome Center, Tartu University Hospital, Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Estonian Genome Center, Tartu University Hospital, Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Reigo
authors.affiliation: Service de Génétique Médicale, CHU-Nantes, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Service de Génétique Médicale, CHU-Nantes, Nantes, France.|INSERM UMR957, Faculté de Médecine, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Le Caignec
authors.affiliation: Service de Génétique Médicale, CHU-Nantes, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: David
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique, Unité Fonctionnelle de Génétique Clinique, Paris, France.|Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, France.|Groupe de Recherche Clinique Déficience Intellectuelle et Autisme, UPMC, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Mignot
authors.affiliation: Groupe Hospitalier Pitié Salpêtrière, AP-HP, Department of Genetics and Cytogenetics, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Keren
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: M B M
authors.initials: MB
authors.lastname: van den Bree
authors.affiliation: Department of Psychology, Clinical Psychology and Psychotherapy, University of Fribourg, Fribourg, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Munsch
authors.affiliation: CIBER Fisiopatologia Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Barcelona, Spain.|Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.|Clinical Sciences Department, School of Medicine, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Fernandez-Aranda
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.|SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Reymond
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Jacquemont
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D056915:DNA Copy Number Variations / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D056344:Executive Function; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012527:Satiation; D017384:Sequence Deletion / Q000235:genetics; D013557:Switzerland