Genetics and Epigenetics in the Obesity Phenotyping Scenario

Overview

Journal Rev Endocr Metab Disord

Publisher Springer

Specialty Endocrinology

Date 2023 Apr 9

PMID 37032403

Authors

Khanh Trang

Struan F A Grant

Affiliations

Soon will be listed here.

Abstract

Obesity is a common complex trait that elevates the risk for various diseases, including type 2 diabetes and cardiovascular disease. A combination of environmental and genetic factors influences the pathogenesis of obesity. Advances in genomic technologies have driven the identification of multiple genetic loci associated with this disease, ranging from studying severe onset cases to investigating common multifactorial polygenic forms. Additionally, findings from epigenetic analyses of modifications to the genome that do not involve changes to the underlying DNA sequence have emerged as key signatures in the development of obesity. Such modifications can mediate the effects of environmental factors, including diet and lifestyle, on gene expression and clinical presentation. This review outlines what is known about the genetic and epigenetic contributors to obesity susceptibility, along with the albeit limited therapeutic options currently available. Furthermore, we delineate the potential mechanisms of actions through which epigenetic changes can mediate environmental influences and the related opportunities they present for future interventions in the management of obesity.

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References

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K . Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016; 375(8):794-8. PMC: 6754861. DOI: 10.1056/NEJMsr1606602. View

Bliddal H, Leeds A, Christensen R . Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons - a scoping review. Obes Rev. 2014; 15(7):578-86. PMC: 4238740. DOI: 10.1111/obr.12173. View

Cummings M, Baldwin M, Abrams D, Jacobson S, Meyer B, Balough E . Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020; 395(10239):1763-1770. PMC: 7237188. DOI: 10.1016/S0140-6736(20)31189-2. View

Bhattacharya I, Ghayor C, Perez Dominguez A, Weber F . From Influenza Virus to Novel Corona Virus (SARS-CoV-2)-The Contribution of Obesity. Front Endocrinol (Lausanne). 2020; 11:556962. PMC: 7573145. DOI: 10.3389/fendo.2020.556962. View

Loos R, Yeo G . The genetics of obesity: from discovery to biology. Nat Rev Genet. 2021; 23(2):120-133. PMC: 8459824. DOI: 10.1038/s41576-021-00414-z. View

Katzmarzyk P, Perusse L, Rao D, Bouchard C . Familial risk of overweight and obesity in the Canadian population using the WHO/NIH criteria. Obes Res. 2000; 8(2):194-7. DOI: 10.1038/oby.2000.21. View

Feinleib M, Garrison R, Fabsitz R, CHRISTIAN J, HRUBEC Z, Borhani N . The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am J Epidemiol. 1977; 106(4):284-5. DOI: 10.1093/oxfordjournals.aje.a112464. View

Stunkard A, Foch T, HRUBEC Z . A twin study of human obesity. JAMA. 1986; 256(1):51-4. View

Stunkard A, Harris J, Pedersen N, McClearn G . The body-mass index of twins who have been reared apart. N Engl J Med. 1990; 322(21):1483-7. DOI: 10.1056/NEJM199005243222102. View

10.

Stunkard A, Sorensen T, Hanis C, Teasdale T, Chakraborty R, Schull W . An adoption study of human obesity. N Engl J Med. 1986; 314(4):193-8. DOI: 10.1056/NEJM198601233140401. View

11.

Locke A, Kahali B, Berndt S, Justice A, Pers T, Day F . Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518(7538):197-206. PMC: 4382211. DOI: 10.1038/nature14177. View

12.

Yengo L, Sidorenko J, Kemper K, Zheng Z, Wood A, Weedon M . Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum Mol Genet. 2018; 27(20):3641-3649. PMC: 6488973. DOI: 10.1093/hmg/ddy271. View

13.

Manolio T, Collins F, Cox N, Goldstein D, Hindorff L, Hunter D . Finding the missing heritability of complex diseases. Nature. 2009; 461(7265):747-53. PMC: 2831613. DOI: 10.1038/nature08494. View

14.

Yengo L, Vedantam S, Marouli E, Sidorenko J, Bartell E, Sakaue S . A saturated map of common genetic variants associated with human height. Nature. 2022; 610(7933):704-712. PMC: 9605867. DOI: 10.1038/s41586-022-05275-y. View

15.

Barres R, Kirchner H, Rasmussen M, Yan J, Kantor F, Krook A . Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep. 2013; 3(4):1020-7. DOI: 10.1016/j.celrep.2013.03.018. View

16.

Nilsson E, Jansson P, Perfilyev A, Volkov P, Pedersen M, Svensson M . Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes. 2014; 63(9):2962-76. DOI: 10.2337/db13-1459. View

17.

Wahl S, Drong A, Lehne B, Loh M, Scott W, Kunze S . Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature. 2016; 541(7635):81-86. PMC: 5570525. DOI: 10.1038/nature20784. View

18.

Snijder M, Zimmet P, Visser M, Dekker J, Seidell J, Shaw J . Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study. Int J Obes Relat Metab Disord. 2004; 28(3):402-9. DOI: 10.1038/sj.ijo.0802567. View

19.

Zhou J, Ge H, Zhu M, Wang L, Chen L, Tan Y . Neck circumference as an independent predictive contributor to cardio-metabolic syndrome. Cardiovasc Diabetol. 2013; 12:76. PMC: 3661343. DOI: 10.1186/1475-2840-12-76. View

20.

Ashwell M, Gunn P, Gibson S . Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev. 2011; 13(3):275-86. DOI: 10.1111/j.1467-789X.2011.00952.x. View