Centers for Disease Control and Prevention. Adult obesity prevalence maps. National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition, Physical Activity, and Obesity; 2023. https://www.cdc.gov/obesity/data/prevalence-maps.html. Accessed 12 Jan 2024.

Stierman B, Afful J, Carroll MD, Chen TC, Davy O, Fink S, Fryar CD, Gu Q, Hales CM, Hughes JP, Ostchega Y. National health and nutrition examination survey 2017–March 2020 prepandemic data files development of files and prevalence estimates for selected health outcomes. Hyattsville, MD: National Health Statistics Reports; 2021. https://doi.org/10.15620/cdc:106273.

Book  Google Scholar 

World Obesity Federation. World Obesity Atlas 2024. https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2024. Accessed 24 Apr 2024.

Couzin-Frankel J. Obesity meets its match. Science. 2023;382(6676):1226–7. https://doi.org/10.1126/science.adn4691.

Article  PubMed  Google Scholar 

Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, Motyer A, Vukcevic D, Delaneau O, O’Connell J, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562(7726):203–9. https://doi.org/10.1038/s41586-018-0579-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

• Backman JD, Li AH, Marcketta A, Sun D, Mbatchou J, Kessler MD, Benner C, Liu D, Locke AE, Balasubramanian S, et al. Exome sequencing and analysis of 454,787 UK Biobank participants. Nature. 2021;599(7886):628–34. https://doi.org/10.1038/s41586-021-04103-z. Paper presents the UKBB sequencing data. This data can be used as controls and for discovery of genetic linkage.

Article  CAS  PubMed  PubMed Central  Google Scholar 

• Ramirez AH, Gebo KA, Harris PA. Progress with the all of us research program: opening access for researchers. JAMA. 2021;325(24):2441–2. https://doi.org/10.1001/jama.2021.7702. Paper presents the progress on All of Us sequencing data. This data can be used as controls and for discovery of genetic linkage.

Article  PubMed  Google Scholar 

FDA News Release. FDA approves first gene therapies to treat patients with sickle cell disease. FDA Newsroom; 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease. Accessed 15 Jan 2024.

Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Investig. 2002;110(8):1093–103. https://doi.org/10.1172/jci0215693.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903–8. https://doi.org/10.1038/43185.

Article  CAS  PubMed  Google Scholar 

Wabitsch M, Funcke JB, von Schnurbein J, Denzer F, Lahr G, Mazen I, El-Gammal M, Denzer C, Moss A, Debatin KM, et al. Severe early-onset obesity due to bioinactive leptin caused by a p.N103K mutation in the leptin gene. J Clin Endocrinol Metab. 2015;100(9):3227–30. https://doi.org/10.1210/jc.2015-2263.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wabitsch M, Funcke JB, Lennerz B, Kuhnle-Krahl U, Lahr G, Debatin KM, Vatter P, Gierschik P, Moepps B, Fischer-Posovszky P. Biologically inactive leptin and early-onset extreme obesity. N Engl J Med. 2015;372(1):48–54. https://doi.org/10.1056/NEJMoa1406653.

Article  CAS  PubMed  Google Scholar 

•• Markham A. Setmelanotide: first approval. Drugs. 2021;81(3):397–403. https://doi.org/10.1007/s40265-021-01470-9. Setmelanotide is a MC4R agonist that is used to treat rare, genetic forms of obesity. This paper discusses the genetic mutations that are appropriate for treatment with the drug.

Article  CAS  PubMed  Google Scholar 

•• Trapp CM, Censani M. Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity. Curr Opin Endocrinol Diabetes Obes. 2023;30(2):136–40. https://doi.org/10.1097/med.0000000000000798. Reviews the use of Setmelanotide treatment in children.

Article  PubMed  PubMed Central  Google Scholar 

AbouHashem N, Zaied RE, Al-Shafai K, Nofal M, Syed N, Al-Shafai M. The spectrum of genetic variants associated with the development of monogenic obesity in qatar. Obes Facts. 2022;15(3):357–65. https://doi.org/10.1159/000521851.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Šket R, Kotnik P, Bizjan BJ, Kocen V, Mlinarič M, Tesovnik T, Debeljak M, Battelino T, Kovač J. Heterozygous genetic variants in autosomal recessive genes of the leptin-melanocortin signalling pathway are associated with the development of childhood obesity. Front Endocrinol (Lausanne). 2022;13:832911. https://doi.org/10.3389/fendo.2022.832911.

Article  PubMed  Google Scholar 

Roberts KJ, Ariza AJ, Selvaraj K, Quadri M, Mangarelli C, Neault S, Davis EE, Binns HJ. Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program. Int J Obes (Lond). 2022;46(8):1493–501. https://doi.org/10.1038/s41366-022-01139-7.

Article  CAS  PubMed  Google Scholar 

Nalbantoğlu Ö, Hazan F, Acar S, Gürsoy S, Özkan B. Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing. J Pediatr Endocrinol Metab. 2022;35(8):1041–50. https://doi.org/10.1515/jpem-2022-0027.

Article  CAS  PubMed  Google Scholar 

Tamaroff J, Williamson D, Slaughter JC, Xu M, Srivastava G, Shoemaker AH. Prevalence of genetic causes of obesity in clinical practice. Obes Sci Pract. 2023;9(5):508–15. https://doi.org/10.1002/osp4.671.

Article  PubMed  PubMed Central  Google Scholar 

Shi P, Shi Y, Liu X, Wang S, Yuan J, Zhao W, Fang L, Wang R, Yan F, Xu C. Identification and characteristics of novel mutations in nonsyndromic monogenic obesity. Adv Biol (Weinh). 2023;7(8):e2300061. https://doi.org/10.1002/adbi.202300061.

Article  CAS  PubMed  Google Scholar 

Roberts KJ, Chaves E, Ariza AJ, Thaker VV, Cho CC, Binns HJ. Exploring genetic testing for rare disorders of obesity: experience and perspectives of pediatric weight management providers. Child Obes. 2024. https://doi.org/10.1089/chi.2023.0125:10.1089/chi.2023.0125.

Article  PubMed  Google Scholar 

Keller M, Svensson SIA, Rohde-Zimmermann K, Kovacs P, Bottcher Y. Genetics and epigenetics in obesity: what do we know so far? Curr Obes Rep. 2023;12(4):482–501. https://doi.org/10.1007/s13679-023-00526-z.

Article  PubMed  PubMed Central  Google Scholar 

Carvalho LML, Jorge AAL, Bertola DR, Krepischi ACV, Rosenberg C. A comprehensive review of syndromic forms of obesity: genetic etiology, clinical features and molecular diagnosis. Curr Obes Rep. 2024. https://doi.org/10.1007/s13679-023-00543-y:10.1007/s13679-023-00543-y.

Article  PubMed  Google Scholar 

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–32. https://doi.org/10.1038/372425a0.

Article  CAS  PubMed  Google Scholar 

Chua SC, Chung WK, WuPeng XS, Zhang YY, Liu SM, Tartaglia L, Leibel RL. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science. 1996;271(5251):994–6. https://doi.org/10.1126/science.271.5251.994.

Article  CAS  PubMed  Google Scholar 

Mahmoud R, Kimonis V, Butler MG. Genetics of obesity in humans: a clinical review. Int J Mol Sci. 2022. https://doi.org/10.3390/ijms231911005.

Article  PubMed  PubMed Central  Google Scholar 

Amaratunga SA, Tayeb TH, Dusatkova P, Pruhova S, Lebl J. Invaluable role of consanguinity in providing insight into paediatric endocrine conditions: lessons learnt from congenital hyperinsulinism, monogenic diabetes, and short stature. Horm Res Paediatr. 2022;95(1):1–11. https://doi.org/10.1159/000521210.

Article  CAS  PubMed  Google Scholar 

Han JC, Liu QR, Jones M, Levinn RL, Menzie CM, Jefferson-George KS, Adler-Wailes DC, Sanford EL, Lacbawan FL, Uhl GR, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med. 2008;359(9):918–27. https://doi.org/10.1056/NEJMoa0801119.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sonoyama T, Stadler LKJ, Zhu M, Keogh JM, Henning E, Hisama F, Kirwan P, Jura M, Blaszczyk BK, DeWitt DC, et al. Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities. Sci Rep. 2020;10(1):9028. https://doi.org/10.1038/s41598-020-65531-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mendes de Oliveira E, Keogh JM, Talbot F, Henning E, Ahmed R, Perdikari A, Bounds R, Wasiluk N, Ayinampudi V, Barroso I, et al. Obesity-associated GNAS mutations and the melanocortin pathway. N Engl J Med. 2021;385(17):1581–92. https://doi.org/10.1056/NEJMoa2103329.

Article  CAS  PubMed  Google Scholar 

Perez KM, Curley KL, Slaughter JC, Shoemaker AH. Glucose homeostasis and energy balance in children with pseudohypoparathyroidism. J Clin Endocrinol Metab. 2018;103(11):4265–74. https://doi.org/10.1210/jc.2018-01067.

Article  PubMed  PubMed Central  Google Scholar 

Roizen JD, Danzig J, Groleau V, McCormack S, Casella A, Harrington J, Sochett E, Tershakovec A, Zemel BS, Stallings VA, et al. Resting energy expenditure is decreased in pseudohypoparathyroidism type 1A. J Clin Endocrinol Metab. 2016;101(3):880–8. https://doi.org/10.1210/jc.2015-3895.

Article  CAS  PubMed  Google Scholar 

Shoemaker AH, Lomenick JP, Saville BR, Wang W, Buchowski MS, Cone RD. Energy expenditure in obese children with pseudohypoparathyroidism type 1a. Int J Obes (Lond). 2013;37(8):1147–53. https://doi.org/10.1038/ijo.2012.200.

Article  CAS  PubMed