The Genetics of Obesity PDF
Preview The Genetics of Obesity
Struan F.A. Grant Editor The Genetics of Obesity The Genetics of Obesity Struan F.A. Grant Editor The Genetics of Obesity Editor Struan F.A. Grant Children’s Hospital of Philadelphia Research Institute Philadelphia, PA, USA ISBN 978-1-4614-8641-1 ISBN 978-1-4614-8642-8 (eBook) DOI 10.1007/978-1-4614-8642-8 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013950488 © Springer Science+Business Media New York 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Contents 1 Genetic Variation and Obesity Prior to the Era of Genome-Wide Association Studies ...................................................... 1 Shana E. McCormack 2 Genetic Obesity Syndromes ..................................................................... 23 I. Sadaf Farooqi and Stephen O’Rahilly 3 Genome-Wide Association Studies of Obesity........................................ 33 Åsa K. Hedman, Cecilia M. Lindgren, and Mark I. McCarthy 4 Copy Number Variants and Their Contribution to the Risk of Obesity ................................................................................ 55 Julia Sarah El-Sayed Moustafa and Philippe Froguel 5 Genetics of Childhood Obesity ................................................................ 71 Struan F. A. Grant 6 Genetic Pleiotropies of Obesity ................................................................ 93 Bratati Kahali and Elizabeth K. Speliotes 7 Functional Follow-up of Genetic Variants Using FTO as the Prime Example ............................................................................... 113 Stefanie Seehaus and Ulrich Rüther Index ................................................................................................................. 127 v Contributors I. Sadaf Farooqi Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science , Addenbrooke’s Hospital , Cambridge , UK Philippe Froguel Department of Genomics of Common Disease , Imperial College London , London , UK Centre National de la Recherche Scientifi que (CNRS)-Unité mixte de recherche de l’Université Lille 2 (UMR) 8199, Lille Pasteur Institute, Lille, France Struan F. A. Grant Division of Human Genetics, The Children’s Hospital of Philadelphia , Philadelphia , PA , USA Department of Pediatrics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Children’s Hospital of Philadelphia Research Institute, Civic Center Blvd, Philadelphia, PA, USA Åsa K. Hedman Wellcome Trust Centre for Human Genetics , University of Oxford , Oxford , UK Bratati Kahali Department of Internal Medicine , Division of Gastroenterology, University of Michigan , Ann Arbor , MI , USA Department of Computational Medicine and Bioinformatics, University of Michigan, Medical Center Drive, Ann Arbor, MI, USA Cecilia M. Lindgren Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge , MA , USA Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK Mark I. McCarthy Wellcome Trust Centre for Human Genetics , University of Oxford, Roosevelt Drive, Oxford , UK vii viii Contributors Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford , Oxford, UK Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK Shana E. McCormack Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia , Philadelphia , PA , USA Julia Sarah El-Sayed Moustafa Department of Genomics of Common Disease , Imperial College London, Hammersmith Hospital , London , UK Stephen O’Rahilly Metabolic Diseases Unit , Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital , Cambridge , UK Ulrich Rüther Institute for Animal Developmental and Molecular Biology , Heinrich-Heine-University , Düsseldorf , Germany Stefanie Seehaus Institute for Animal Developmental and Molecular Biology , Heinrich-Heine-University , Düsseldorf , Germany Elizabeth K. Speliotes Department of Internal Medicine , Division of Gastroenterology, University of Michigan , Ann Arbor , MI , USA Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA Chapter 1 Genetic Variation and Obesity Prior to the Era of Genome-Wide Association Studies Shana E. McCormack Abstract The purpose of this chapter is to present a comprehensive review of the evidence for how genetic variation contributes to common obesity (which we have chosen to defi ne as affecting >1 % of obese individuals, likely non-syndromic in etiology, and related to diet and inactivity) in the general population prior to the era of genome wide association studies (GWAS). Twin and adoption studies demon- strate that the tendency to be obese is highly heritable, and also suggest that the cumulative effect of gene–environment interactions on body mass index (BMI) seems to increase with age. Before GWAS, one common approach to dissecting the role of genetic variability in common obesity was to investigate candidate genes. Some of the genes implicated in monogenic or syndromic obesity by traditional linkage anal- ysis, for example, M C4R , have milder variants that appear to be important in com- mon obesity as well. By 2004, over 600 candidate genes or chromosomal regions had been implicated in the pathogenesis of obesity, and 18 of these had multiple lines of supporting evidence. Despite this, much of the heritability in obesity remained to be explained. Next-g eneration sequencing technology should produce additional insights that extended these seminal investigations but despite this, much of the so-called missing heritability identifi ed prior to the era of GWAS persists. The global prevalence of obesity has risen rapidly, in particular during the latter part of the twentieth century and the beginning of the twenty-fi rst century. Obesity became a World Health Organization priority after its signifi cant contribution to cardiovascular disease burden as well as all-cause mortality from other conditions, including cancer, came to be appreciated [1 ]. In the USA, the harbinger of the global S. E. McCormack , M.D. (*) Division of Endocrinology and Diabetes , Children’s Hospital of Philadelphia , 34th and Civic Center Boulevard, Suite 11NW30 , Philadelphia , PA 19104 , USA e-mail: [email protected] S.F.A. Grant (ed.), The Genetics of Obesity, DOI 10.1007/978-1-4614-8642-8_1, 1 © Springer Science+Business Media New York 2014
The list of books you might like
