Genetics of Obesity

  • Lotte Kleinendorst
  • Mieke M. van Haelst
  • Erica L. T. van den AkkerEmail author
Part of the Experientia Supplementum book series (EXS, volume 111)


Obesity is caused by an imbalance between energy intake and output, influenced by numerous environmental, biological, and genetic factors. Only a minority of people with obesity have a genetic defect that is the main cause of their obesity. A key symptom for most of these disorders is early-onset obesity and hyperphagia. For some genetic obesity disorders, the hyperphagia is the main characteristic, often caused by disruptions of the leptin-melanocortin pathway, the central pathway that regulates the body’s satiety and energy balance. For other disorders, obesity is part of a distinct combination of other clinical features such as intellectual disability, dysmorphic facial features, or organ abnormalities. This chapter focuses on genetic obesity disorders and also summarizes the present knowledge on the genetics of the more common polygenic/multifactorial obesity.


Body weight regulation Common obesity Early-onset obesity Hyperphagia Leptin-melanocortin pathway Genetic obesity Non-syndromic obesity Syndromic obesity 



Adrenocorticotropic hormone


Agouti-related protein


Albright hereditary osteodystrophy


Bardet-Biedl syndrome


Body mass index




Glucagon-like peptide-1


Intellectual disability


Melanocortin 3 receptor


Melanocortin 4 receptor


Melanocyte-stimulating hormone


Neuropeptide Y


Pseudohypoparathyroidism type 1a




Prader-Willi syndrome


Peptide YY


Uniparental disomy


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Lotte Kleinendorst
    • 1
    • 2
    • 3
  • Mieke M. van Haelst
    • 2
    • 3
  • Erica L. T. van den Akker
    • 1
    • 4
    Email author
  1. 1.Obesity Center CGG, Erasmus MC, University Medical CenterRotterdamThe Netherlands
  2. 2.Department of Clinical GeneticsAmsterdam UMC, Location AMCAmsterdamThe Netherlands
  3. 3.Department of Clinical GeneticsAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
  4. 4.Division of Endocrinology, Department of PediatricsErasmus MC-Sophia Children’s Hospital, University Medical CenterRotterdamThe Netherlands

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