16p11.2 Locus modulates response to satiety before the onset of obesity

• Published in: International Journal of Obesity Vol. 40; no. 5; pp. 870 - 876
• Main Authors: Maillard, A M, Hippolyte, L, Rodriguez-Herreros, B, Chawner, S J R A, Dremmel, D, Agüera, Z, Fagundo, A B, Pain, A, Martin-Brevet, S, Hilbert, A, Kurz, S, Etienne, R, Draganski, B, Jimenez-Murcia, S, Männik, K, Metspalu, A, Reigo, A, Isidor, B, Le Caignec, C, David, A, Mignot, C, Keren, B, van den Bree, M B M, Munsch, S, Fernandez-Aranda, F, Beckmann, J S, Reymond, A, Jacquemont, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2016; Nature Publishing Group
• Subjects: 692/699; Adolescents; Adult; Adults; Autism; Autistic Disorder - complications; Autistic Disorder - genetics; Autistic Disorder - physiopathology; Binge eating; Body Mass Index; Body size; Bulimia; Case-Control Studies; Child; Children; Chromosome 16; Chromosome Deletion; Chromosome Disorders - complications; Chromosome Disorders - genetics; Chromosome Disorders - physiopathology; Chromosomes, Human, Pair 16 - genetics; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - etiology; Cognitive Dysfunction - genetics; Cognitive Dysfunction - physiopathology; Copy number; Copy number variations; Deletion; Development and progression; DNA Copy Number Variations - genetics; Eating behavior; Eating disorders; Energy Metabolism - genetics; Energy Metabolism - physiology; Epidemiology; Executive Function; Feeding Behavior - physiology; Female; Food habits; Gene dosage; Genetic aspects; Genetic Predisposition to Disease; Genetic research; Genomics; Health aspects; Health Promotion and Disease Prevention; Humans; Intellectual Disability - complications; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Internal Medicine; Loci; Malalties mentals; Male; Medicine; Medicine & Public Health; Mental disorders; Mental illness; Metabolic Diseases; Neurosciences; Obesitat; Obesity; Obesity - etiology; Obesity - genetics; Obesity - physiopathology; original-article; Pediatrics; Phenotype; Psychological aspects; Psychology; Public Health; Reproduction (copying); Satiation; Satiety; Schizophrenia; Sequence Deletion - genetics; Switzerland; Underweight; Switzerland; France; Germany; Paris France; Spain
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2015.247

Background: 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. Objective: This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs. Methods: 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. Results: 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. Conclusions: 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.