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Genetics of Obesity

Updated: Jun 14, 2023

By: Fiona Yue


The debate over nature versus nurture extends to the topic of obesity. Obesity is defined by a BMI over 30 and currently, 42.4% of adults and 19.3% of adolescents and children ages 2-19 are obese in the U.S. These individuals are more at risk for obesity-related conditions like type 2 diabetes, cancer, high blood pressure, high cholesterol, asthma, sleep apnea, joint problems, etc. But, not only can it cause preventable conditions that can lead to premature death, it is also extremely costly. Obese adults usually pay $1,861 more in medical bills compared with individuals of a healthy weight. This begs the question: what causes obesity?


There are genetic factors that can cause obesity. Monogenic, or single gene, mutations that code for proteins like leptin, the leptin receptor, pro-opiomelanocortin, and the melanocortin-4 receptor can affect appetite control, metabolism, and food intake. More commonly, polygenic, or multiple gene, mutations contribute to obesity. Such genes include CYP27A1, TFAP2B, PARK2, IFNGR1, UCP2, and UCP3 (together code for body fat), ADRB1-3 (affects energy utilization and lipolysis), SLC6A14 (affects appetite control and energy balance), and the FTO gene (affects satiety, activity, and body fat) present in 43% of the population. Furthermore, histone acetylation and methylation can affect body fat, such as modifying the adipogenesis genes: Pref-1, c/EBP beta, C/EBP alpha, PPAR gamma, and aP2. These polygenic mutations increase the risk of obesity by 20-30%. Obesity is also syndromic, present in symptoms of genetic disorders like Prader–Willi, caused by a mutation on chromosome 15, or Bardet-Biedl syndrome, caused by a combination of multiple genes.


However, genes alone cannot explain the prediction of 51% of the world population being overweight/obese within the next 12 years. These mutations take generations to spread so “nurture” must play a role. Nowadays, food, especially highly processed foods, fast food, and sugar-sweetened beverages, is readily available anytime, anywhere. People are also becoming less active, with 25% of people working from home and children spending more time watching television or using devices. These lifestyles cause individuals to overeat while remaining sedentary, greatly increasing the likelihood of obesity.


In a study involving the FTO rs9939609 variant, adults with this risk allele had an increased odds for obesity by 1.23-fold. However, if the adult was physically active, they only had an increased chance by 1.22-fold compared to physically inactive adults, who had an increased chance by 1.30-fold. By being physically active, the genetically susceptible adults lowered their risk by 27%. In an earlier study done with the same SNP, the results showed a 1.95 +/- 0.33 kg/m2 increase in BMI for physically inactive adults with the risk allele versus without. By making lifestyle changes, individuals are able to overcome their genetic disposition for obesity.


References:

"Overweight & Obesity Statistics - NIDDK.” National Institute of Diabetes and Digestive and Kidney Diseases, https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity.


Loos, Ruth J. F., and Giles S. H. Yeo. “The Genetics of Obesity: From Discovery to Biology.” Nature Reviews Genetics, vol. 23, no. 2, Feb. 2022, pp. 120–33.


Avenue, 677 Huntington, et al. “Genes Are Not Destiny.” Obesity Prevention Source, 21 Oct. 2012, https://www.hsph.harvard.edu/obesity-prevention-source/obesity-causes/genes-and-obesity/.


Tirthani, Ekta, et al. “Genetics and Obesity.” StatPearls, StatPearls Publishing, 2023. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK573068/.


Obesity and Genetics - Nature - Nurture - Obesity Medicine Association. 23 July 2018, https://obesitymedicine.org/obesity-and-genetics/.


KilpelinenTO, Qi L, Brage S, et al.Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med. 2011. Epub 2011 Nov 1.


Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes. 2008; 57:95-101.


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