A Common Genetic Variant Is Associated with Adult and Childhood Obesity

Alan Herbert; Norman P. Gerry; Matthew B. McQueen; Iris M. Heid; Arne Pfeufer; Thomas Illig; H.-Erich Wichmann; Thomas Meitinger; David Hunter; Frank B. Hu; Graham Colditz; Anke Hinney; Johannes Hebebrand; Kerstin Koberwitz; Xiaofeng Zhu; Richard Cooper; Kristin Ardlie; Helen Lyon; Joel N. Hirschhorn; Nan M. Laird; Marc E. Lenburg; Christoph Lange; Michael F. Christman

doi:10.1126/science.1124779

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A Common Genetic Variant Is Associated with Adult and Childhood Obesity

Alan Herbert1,*,
Norman P. Gerry1,
Matthew B. McQueen2,
Iris M. Heid3,4,
Arne Pfeufer5,6,
Thomas Illig3,4,
H.-Erich Wichmann3,4,7,
Thomas Meitinger5,6,
David Hunter2,8,9,
Frank B. Hu2,8,9,
Graham Colditz8,9,
Anke Hinney10,
Johannes Hebebrand10,
Kerstin Koberwitz6,10,
Xiaofeng Zhu11,
Richard Cooper11,
Kristin Ardlie12,
Helen Lyon13,14,15,
Joel N. Hirschhorn13,14,15,
Nan M. Laird16,
Marc E. Lenburg1,
Christoph Lange9,13,
Michael F. Christman1,*

¹ Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA.
² Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
³ Institute of Epidemiology, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.
⁴ KORA Group, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.
⁵ Institute of Human Genetics, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.
⁶ Institute of Human Genetics, Technical University Munich, D-81671 Munich, Germany.
⁷ Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany.
⁸ Nurses Health Study, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
⁹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
¹⁰ Department of Child and Adolescent Psychiatry of the University of Duisburg-Essen, D-45147 Essen, Germany.
¹¹ Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL 60153, USA.
¹² Genomics Collaborative, SeraCare Life Sciences, Cambridge, MA, USA.
¹³ Program in Genomics and Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA.
¹⁴ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
¹⁵ Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.
¹⁶ Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.

↵* To whom correspondence should be addressed. E-mail: aherbert{at}bu.edu (A.H.); mfc{at}bu.edu (M.F.C.)

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Science 14 Apr 2006:
Vol. 312, Issue 5771, pp. 279-283
DOI: 10.1126/science.1124779

Alan Herbert

Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA.

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For correspondence: aherbert@bu.edu mfc@bu.edu

Norman P. Gerry

Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA.

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Matthew B. McQueen

Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.

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Iris M. Heid

Institute of Epidemiology, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany. KORA Group, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.

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Arne Pfeufer

Institute of Human Genetics, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany. Institute of Human Genetics, Technical University Munich, D-81671 Munich, Germany.

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Thomas Illig

Institute of Epidemiology, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany. KORA Group, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.

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H.-Erich Wichmann

Institute of Epidemiology, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany. KORA Group, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany. Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany.

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Thomas Meitinger

Institute of Human Genetics, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany. Institute of Human Genetics, Technical University Munich, D-81671 Munich, Germany.

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David Hunter

Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Nurses Health Study, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.

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Frank B. Hu

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Graham Colditz

Nurses Health Study, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.

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Anke Hinney

Department of Child and Adolescent Psychiatry of the University of Duisburg-Essen, D-45147 Essen, Germany.

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Johannes Hebebrand

Department of Child and Adolescent Psychiatry of the University of Duisburg-Essen, D-45147 Essen, Germany.

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Kerstin Koberwitz

Institute of Human Genetics, Technical University Munich, D-81671 Munich, Germany. Department of Child and Adolescent Psychiatry of the University of Duisburg-Essen, D-45147 Essen, Germany.

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Xiaofeng Zhu

Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL 60153, USA.

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Richard Cooper

Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL 60153, USA.

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Kristin Ardlie

Genomics Collaborative, SeraCare Life Sciences, Cambridge, MA, USA.

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Helen Lyon

Program in Genomics and Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.

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Joel N. Hirschhorn

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Nan M. Laird

Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.

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Marc E. Lenburg

Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA.

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Christoph Lange

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. Program in Genomics and Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA.

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Michael F. Christman

Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA.

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For correspondence: aherbert@bu.edu mfc@bu.edu

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Abstract

Obesity is a heritable trait and a risk factor for many common diseases such as type 2 diabetes, heart disease, and hypertension. We used a dense whole-genome scan of DNA samples from the Framingham Heart Study participants to identify a common genetic variant near the INSIG2 gene associated with obesity. We have replicated the finding in four separate samples composed of individuals of Western European ancestry, African Americans, and children. The obesity-predisposing genotype is present in 10% of individuals. Our study suggests that common genetic polymorphisms are important determinants of obesity.

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A Common Genetic Variant Is Associated with Adult and Childhood Obesity

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