Research Chair on Obesity Centre de recherche Institut Universitaire de Cardiologie et de Pneumologie du QuébecUniversité Laval
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Etiology

Genetic factors of overweight and obesity

How do genes affect obesity?

SUMMARY: Science shows that genetics plays a role in obesity. Genes can directly cause obesity in disorders such as Bardet-Biedl syndrome and Prader-Willi syndrome. However genes do not always predict future health. Genes and behavior may both be needed for a person to be overweight. In some cases multiple genes may increase one’s susceptibility for obesity and require outside factors; such as abundant food supply or little physical activity.

Obesity is a complex disease resulting from the interactions of a wide variety of hereditary and environmental factors. The combined progress in quantitative genetics, genomics and bioinformatics has contributed to a better understanding of the genetic and molecular basis of obesity.

Clustering of cases within a family, the congruence of body weight for monozygotic twins, and the discovery of genes associated with obesity are all arguments reinforcing the genetic dimension of obesity

It is now well established that overweight and the different forms of obesity are conditions tending to concentrate within a family. Obesity risk is two to eight times higher for a person with a family history as opposed to a person with no family history of obesity, and an even higher risk is observed in cases of severe obesity. Heritability of obesity may vary depending on the phenotype studied, however it tends to be higher for phenotypes linked to adipose tissue distribution (40-55%) and for weight or body fat excess (5-40%). Weight gain and adiposity increase with age, an effect also influenced by heredity.

Occurrences of monogenic types of obesity are evidence that obesity may be caused by genetic mutations, however, as yet, only 78 cases worldwide have been attributed to mutations of seven distinct genes. The most common forms of obesity are probably the result of variations within a large number of genes. Sequence variations within a pool of 56 different genes have been reported as being related to obesity phenotypes, however, only ten of those genes showed positive results in at least five different studies.

Beside these rare cases, many individuals have a genetic predisposition that may lead to obesity. Researchers have found many obesity susceptibility genes and the combination of an obesogenic environment and a genetic predisposition will almost inescapably result in the development of obesity. However, it is possible to be obese without having a genetic predisposition.

In brief, current knowledge brings to the conclusion that genetic factors may be involved in the etiology of obesity and, exclusive of very rare severe obesity cases, the genes involved are probably genes that interact with environment factors related to energy intake and expenditure to increase the risk of obesity.

Identification of those genes will help clarify the etiology of obesity and its metabolic consequences, the metabolic complications of obesity, as well as identify at-risk individuals or groups in terms of their genetic profile with the goal of developing personalized prevention and treatment strategies.

For more information on the genetics and obesity visit Obesity and Genetics: A Public Health Perspective.




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