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Published Online April 12, 2007
Science DOI: 10.1126/science.1141634

Reports

Submitted on February 22, 2007
Accepted on April 6, 2007

A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity

Timothy M. Frayling 1, Nicholas J. Timpson 2, Michael N. Weedon 1, Eleftheria Zeggini 3, Rachel M. Freathy 1, Cecilia M. Lindgren 3, John R. B. Perry 1, Katherine S. Elliott 4, Hana Lango 1, Nigel W. Rayner 3, Beverley Shields 5, Lorna W. Harries 5, Jeffrey C. Barrett 4, Sian Ellard 6, Christopher J. Groves 7, Bridget Knight 5, Ann-Marie Patch 6, Andrew R. Ness 8, Shah Ebrahim 9, Debbie A. Lawlor 10, Susan M. Ring 10, Yoav Ben-Shlomo 10, Marjo-Riitta Jarvelin 11, Ulla Sovio 11, Amanda J. Bennett 7, David Melzer 12, Luigi Ferrucci 13, Ruth J. F. Loos 14, Inês Barroso 15, Nicholas J. Wareham 14, Fredrik Karpe 7, Katharine R. Owen 7, Lon R. Cardon 4, Mark Walker 16, Graham A. Hitman 17, Colin N. A. Palmer 18, Alex S. F. Doney 19, Andrew D. Morris 19, George Davey-Smith 20, The Wellcome Trust Case Control Consortium 21, Andrew T. Hattersley 1*, Mark I. McCarthy 3

1 Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK; Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, UK.
2 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK; The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Rd, Bristol, UK.
3 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
4 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
5 Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, UK.
6 Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, UK; The Molecular Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Old Pathology Building, Barrack Road, Exeter, UK.
7 Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
8 Department of Oral & Dental Science, Lower Maudlin Street, Bristol, UK.
9 Department of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK.
10 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, UK.
11 Department of Epidemiology and Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK; Department of Public Health Science and General Practice, Fin-90014, University of Oulu, Finland.
12 Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK; Epidemiology and Public Health Group, Peninsula Medical School, Barrack Road, Exeter, UK.
13 Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
14 MRC Epidemiology Unit, Strangeways Research Laboratories, Cambridge, UK.
15 Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
16 Diabetes Research Group, School of Clinical Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.
17 Centre for Diabetes and Metabolic Medicine, Barts and The London, Royal London Hospital, Whitechapel, London, UK.
18 Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK.
19 Diabetes Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.
20 The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Rd, Bristol, UK.
21 Membership of the Wellcome Trust Case Control Consortium is listed in the Supporting Online Material.

* To whom correspondence should be addressed.
Andrew T. Hattersley , E-mail: Andrew.Hattersley{at}pms.ac.uk

Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes susceptibility genes identified a common variant in the FTO gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had a 1.67-fold increased risk of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.


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