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Human SH2B1 mutations are associated with maladaptive behaviors and obesity
Michael E. Doche,1 Elena G. Bochukova,2 Hsiao-Wen Su,1 Laura R. Pearce,2 Julia M. Keogh,2 Elana Henning,2 Joel M. Cline,1 Sadia Saeed,2 Anne Dale,3 Tim Cheetham,4 Inês Barroso,2,5 Lawrence S. Argetsinger,1 Stephen O’Rahilly,2 Liangyou Rui,1 Christin Carter-Su,1 and I. Sadaf Farooqi2
1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 2University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. 3Queen Elizabeth Hospital, Gateshead, United Kingdom. 4Royal Victoria Infirmary and Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
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Published January 2, 2013 - More info
J Clin Invest. 2013;123(1):526–526. https://doi.org/10.1172/JCI68022.
© 2013 The American Society for Clinical Investigation
Related article:
Abstract
Src homology 2 B adapter protein 1 (SH2B1) modulates signaling by a variety of ligands that bind to receptor tyrosine kinases or JAK-associated cytokine receptors, including leptin, insulin, growth hormone (GH), and nerve growth factor (NGF). Targeted deletion of Sh2b1 in mice results in increased food intake, obesity, and insulin resistance, with an intermediate phenotype seen in heterozygous null mice on a high-fat diet. We identified SH2B1 loss-of-function mutations in a large cohort of patients with severe early-onset obesity. Mutation carriers exhibited hyperphagia, childhood-onset obesity, disproportionate insulin resistance, and reduced final height as adults. Unexpectedly, mutation carriers exhibited a spectrum of behavioral abnormalities that were not reported in controls, including social isolation and aggression. We conclude that SH2B1 plays a critical role in the control of human food intake and body weight and is implicated in maladaptive human behavior.
Authors
Michael E. Doche, Elena G. Bochukova, Hsiao-Wen Su, Laura R. Pearce, Julia M. Keogh, Elana Henning, Joel M. Cline, Anne Dale, Tim Cheetham, Inês Barroso, Lawrence S. Argetsinger, Stephen O’Rahilly, Liangyou Rui, Christin Carter-Su, I. Sadaf Farooqi
Original citation: J. Clin. Invest. 2012;122(12):4732–4736. doi:10.1172/JCI62696.
Citation for this corrigendum: J. Clin. Invest. 2013;123(1):526. doi:10.1172/JCI68022.
Sadia Saeed was inadvertently omitted from the author list. The correct author and affiliation lists are above.
The authors regret the error.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)