Genetics of obesity
Like many other medical conditions, obesity is the result of an interplay between genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose to obesity under certain dietary conditions. The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, from 6% to 85%. As of 2006, more than 41 sites on the human genome have been linked to the development of obesity when a favorable environment is present. The involvement of genetic factors in the development of obesity is estimated to be 40–70%. Some of these obesogenic or leptogenic genes may influence obese individuals response to weight loss or weight management.
Confirmed and hypothesized associations include:
|leptin receptor deficiency||601007||1p31|
|prohormone convertase-1 deficiency||600955||5q15-q21|
|melanocortin-4 receptor polymorphism (MC4R)||155541||18q22|
|BMIQ3||6q23-q25||near D6S1009, GATA184A08, D6S2436, and D6S305|
|BMIQ4||11q24||near D11S1998, D11S4464, and D11S912|
|FTO||16q12.2||Adults who were homozygous for a particular FTO allele weighed about 3 kilograms more and had a 1.6-fold greater rate of obesity than those who had not inherited this trait. This association disappeared, though, when those with FTO polymorphisms participated in moderately intensive physical activity equivalent to three to four hours of brisk walking.|
|KCTD15||19q13.12||KCTD15 plays a role in transcriptional repression of AP-2α, which in turn, inhibits the activity of C/EBPα, an early inducer of adipogenesis.|
Some studies have focused upon inheritance patterns without focusing upon specific genes. One study found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.
The thrifty gene hypothesis postulates that due to dietary scarcity during human evolution people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima Indians, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.
Numerous studies of laboratory rodents provide strong evidence that genetics plays an important role in obesity.
The risk of obesity is determined by not only specific genotypes but also gene-gene interactions. However, there are still challenges associated with detecting gene-gene interactions for obesity.
Obesity is also a maior feature in several syndromes, such as Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, Ayazi syndrome, and MOMO syndrome. (The term "non-syndromic obesity" is sometimes used to exclude these conditions.) In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.
- Mary Jones. "Case Study: Cataplexy and SOREMPs Without Excessive Daytime Sleepiness in Prader Willi Syndrome. Is This the Beginning of Narcolepsy in a Five Year Old?". European Society of Sleep Technologists. Retrieved April 6, 2009.
- Albuquerque D, Stice E, et al. (Mar 2015). "Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective". Mol. Genet. Genomics. doi:10.1007/s00438-015-1015-9. PMID 25749980.
- Yang W, Kelly T, He J (2007). "Genetic epidemiology of obesity". Epidemiol Rev 29: 49–61. doi:10.1093/epirev/mxm004. PMID 17566051.
- Poirier P, Giles TD, Bray GA, et al. (May 2006). "Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss". Arterioscler. Thromb. Vasc. Biol. 26 (5): 968–76. doi:10.1161/01.ATV.0000216787.85457.f3. PMID 16627822.
- Hainer, Vojtĕch; Hermann Toplak; Asimina Mitrakou (February 2008). "Treatment Modalities of Obesity: What fits whom?". Diabetes Care 31: 269–277. doi:10.2337/dc08-s265.
- Lee YS (January 2009). "The role of leptin-melanocortin system and human weight regulation: lessons from experiments of nature" (PDF). Ann. Acad. Med. Singap. 38 (1): 34–11. PMID 19221669. Retrieved 2009-06-08.
- Willer CJ, Speliotes EK, Loos RJ, et al. (January 2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nat. Genet. 41 (1): 25–34. doi:10.1038/ng.287. PMC 2695662. PMID 19079261.
- "OMIM - OBESITY". Retrieved 2009-06-08.
- Zhao J, Bradfield JP, Li M, et al. (May 2009). "The role of obesity-associated loci identified in genome wide association studies in the determination of pediatric BMI". Obesity (Silver Spring) 17 (12): 2254–7. doi:10.1038/oby.2009.159. PMC 2860782. PMID 19478790.
- Feitosa MF, Borecki IB, Rich SS, et al. (January 2002). "Quantitative-Trait Loci Influencing Body-Mass Index Reside on Chromosomes 7 and 13: The National Heart, Lung, and Blood Institute Family Heart Study". Am. J. Hum. Genet. 70 (1): 72–82. doi:10.1086/338144. PMC 384905. PMID 11713718.
- Atwood LD, Heard-Costa NL, Cupples LA, Jaquish CE, Wilson PW, D'Agostino RB (November 2002). "Genomewide Linkage Analysis of Body Mass Index across 28 Years of the Framingham Heart Study". Am. J. Hum. Genet. 71 (5): 1044–50. doi:10.1086/343822. PMC 385083. PMID 12355400.
- Gorlova OY, Amos CI, Wang NW, Shete S, Turner ST, Boerwinkle E (June 2003). "Genetic linkage and imprinting effects on body mass index in children and young adults". Eur. J. Hum. Genet. 11 (6): 425–32. doi:10.1038/sj.ejhg.5200979. PMID 12774034.
- Frayling TM, Timpson NJ, Weedon MN, et al. (2007). "A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity". Science 316 (5826): 889–94. doi:10.1126/science.1141634. PMC 2646098. PMID 17434869.
- Rampersaud E, Mitchell BD, Pollin TI, et al. (2008). "Physical activity and the association of common FTO gene variants with body mass index and obesity". Arch Intern Med 16 (16): 1791–97. doi:10.1001/archinte.168.16.1791. PMID 18779467.
- Skoblov, Mikhail; Andrey Marakhonov; Ekaterina Marakasova; Anna Guskova; Vikas Chandhoke; Aybike Birerdinc; Ancha Baranova (2013). "Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development". BioEssays 35 (7): 586–596. doi:10.1002/bies.201300002. PMID 23592240.
- Renström F, Payne F, Nordström A, et al. (April 2009). "Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden". Hum. Mol. Genet. 18 (8): 1489–96. doi:10.1093/hmg/ddp041. PMC 2664142. PMID 19164386.
- Meyre, David; Delplanque, Jérôme; Chèvre, Jean-Claude; Lecoeur, CéCile; Lobbens, StéPhane; Gallina, Sophie; Durand, Emmanuelle; Vatin, Vincent; et al. (18 January 2009). "Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations". Nature Genetics 41 (2): 157–9. doi:10.1038/ng.301. PMID 19151714.
- Kolata,Gina (2007). Rethinking thin: The new science of weight loss - and the myths and realities of dieting. Picador. p. 122. ISBN 0-312-42785-9.
- Chakravarthy MV, Booth FW (2004). "Eating, exercise, and "thrifty" genotypes: Connecting the dots toward an evolutionary understanding of modern chronic diseases". J. Appl. Physiol. 96 (1): 3–10. doi:10.1152/japplphysiol.00757.2003. PMID 14660491.
- Wells JC (February 2009). "Ethnic variability in adiposity and cardiovascular risk: the variable disease selection hypothesis". Int J Epidemiol 38 (1): 63–71. doi:10.1093/ije/dyn183. PMID 18820320.
- Garland Jr, Theodore; Schutz, Heidi; Chappell, Mark A.; Keeney, Brooke K.; Meek, Thomas H.; Copes, Lynn E.; Acosta, Wendy; Drenowatz, Clemens; Maciel, Robert C.; van Dijk, Gertjan; Kotz, Catherine M.; Eisenmann, Joey C. (2011). "The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives". J. Exp. Biol. 214 (2): 206–29. doi:10.1242/jeb.048397. PMC 3008631. PMID 21177942.
- Yang, Wenjie; Tanika Kelly; Jiang He (June 12, 2007). "Genetic Epidemiology of Obesity". Epidemiologic Reviews 29: 49–61. doi:10.1093/epirev/mxm004. PMID 17566051.
- Walley AJ, Asher JE, Froguel P (June 2009). "The genetic contribution to non-syndromic human obesity". Nat. Rev. Genet. 10 (7): 431–42. doi:10.1038/nrg2594. PMID 19506576.
- Farooqi S, O'Rahilly S; o’Rahilly, Stephen (December 2006). "Genetics of obesity in humans". Endocr. Rev. 27 (7): 710–18. doi:10.1210/er.2006-0040. PMID 17122358.