How Can I Calculate My Genetic Risk for Obesity?

Is My Risk for Obesity Inherited?

Obesity occurs for many reasons, some of which are environmental (e.g., the foods we eat, sedentary behaviors, insufficient sleep), whereas others are genetic (i.e., the risk we inherit because of being born into a particular family). Your risk for developing obesity increases with the presence of obesity in your parents and family. About 60% to 90% of the risk for obesity is inherited (Snyder et al, 2004; Perusse et al, 2005), which means that much of the predisposition to become overweight lies in your genes. If one of your parents’ struggles with

overweight, your risk is two to three times greater than someone who has two lean parents, and it increases about 15-fold if both of your parents suffer from obesity (Whitaker et al, 1997).

Genetic variability can contribute to differences in basic metabolic rate (e.g., how you burn calories), the effects of exercise on weight loss, the utilization of calories, and the response to different kinds of diets on weight-loss efforts. In addition, there are genetic factors that modify your risk of developing complications related to overweight, such as diabetes, hypertension, heart disease, and kidney disease (Shu et al, 2017).

There are two different kinds of genetic predispositions. With one type, there is an identified defect (mutation) in a single gene of your DNA that alters the function of that gene. These mutations can be spontaneous (i.e., no defect was present in either parent, but the defective gene can be identified in the person suffering from that disease) or these can be transmitted down generations in a specific manner, such as autosomal recessive or autosomal dominant (this means that there might be a minor or major contribution to your weight based upon your genes). Less than 1% of obesity is caused by a single gene defect (Reinehr et al, 2007). These single gene defects include certain types of obesity (caused by proopiomelanocortin [POMC] mutations, leptin deficiency, Prader-Willi syndrome, Bardet-Biedl syndrome) that are inherited in this way. In most instances, the mutated gene is identified by testing. However, because these disorders have a miniscule contribution to the overall prevalence of obesity, they are investigated only when your doctor highly suspects that your obesity has some unique features of these diseases, in addition to obesity.

On the other hand, the more common form of obesity that is caused by caloric excess does not have a single identified and affected gene. This form of obesity, also referred to as exogenous obesity, also has a strong genetic predisposition that is attributed to numerous small changes in the whole genome. A recent study suggests that there are about 100 different loci (small regions on the DNA) that can be altered to affect the body mass index (BMI) (Locke et al, 2015). The contribution of these identified genes to changes in BMI is about 20% (Locke et al, 2015). 

Unfortunately, there is no commercially available test that looks for these genetic changes. However, there is one gene on chromosome 16 that has gained the most attention: the fat mass and obesity gene, commonly known as the FTO gene (Fawcett and Barrosso, 2010). The clear role of the FTO gene in causing obesity is still being explored. However, studies suggest that alterations in the FTO gene might change the role of some fat cells from using energy to storing energy and slowing down the caloric utilization by thermogenesis (Claussnitzer et al, 2015).

How Do I Inherit Genes That Contribute to Obesity?

Genes are the DNA structures that make up chromosomes. When conception occurs, half of the genes come from the mother and half come from the father. For the most part, an individual has two copies of a single gene, one from each parent. The physical expression of the gene depends on its dominance (i.e., the more active and stronger the gene, the greater is its expression); sometimes, both genes work equally (called autosomal recessive).

There is no one gene that controls the common form of obesity. Scientists have identified many different changes in the DNA that might be associated with the risk of developing obesity, and these small variations are called single nucleotide polymorphisms (SNPs). These are small components that alter the function of the gene slightly, but they do not cause a major disruption in its function. These small changes accrue over generations and are then transferred from parents to offspring.

How Will I Know Whether My Family Has an Inherited Risk for Obesity?

If multiple members of your family have struggled with weight for generations, your family likely has the inherited risk of developing obesity. However, it is difficult to know which alterations in the genome are unique to your family. Knowledge of those unique alterations might not have a meaningful impact on your treatment, given that we do not yet know how to reverse these DNA changes.

On the other hand, if you are diagnosed with one of those rare cases of obesity that are caused by single gene defects, certain laboratories can test for this. Tests can also be run on your family members to find out whether they also carry these gene defects.

Which Types of Obesity Are Linked with an Inherited Risk?

Most types of obesity have a genetic predisposition. However, the genetic risk varies with the kind of obesity that you have. As mentioned previously, the rare forms of obesity that have a single identified abnormal gene have a more discrete type of inheritance.

Single gene disorders with obesity as a major trait include the following:

Melanocortin-4 receptor deficiency (MC-4R)

This is the most common cause of obesity associated with a single gene. It can be caused by defects in only one gene (from one parent [heterozygous]) or in both genes (from both parents [homozygous]).

Leptin deficiency

This is an autosomal recessive condition, in which both genes have a mutation. This typically results in a voracious appetite, high insulin levels, insulin resistance, and infertility.

Leptin receptor deficiency

This is an autosomal recessive condition.

Prohormone convertase-1 deficiency (PCSK1)

This condition involves defects in the production of many hormones. Genetic variability in the gene has been identified.

POMC deficiency

Patients with this condition also have adrenal insufficiency. Genetic changes in both genes have been found.

Syndromes for which obesity is one of the features:

Prader-Willi syndrome

This syndrome is caused by abnormalities in the long arm of chromosome 15. This is the most common syndromic form of obesity. It presents with difficulty feeding at birth and poor muscle tone as a child. There are many behavioral issues, developmental delays, short height, and hypogonadism.

Bardet-Biedel syndrome

This is an autosomal recessive condition in which both genes are affected. It is associated with intellectual disability, vision issues, and kidney problems.

Alstrom syndrome

This is a rare autosomal recessive disorder. It usually presents very early in life.

Should I Discuss Genetic Testing with My Doctor?

You should discuss the need for genetic testing with your doctor. However, it is important to realize that the most common kind of obesity does not have a single gene identified as a cause of the obesity. However, the risk of obesity is greater if both parents have obesity than if only one is obese. Although there are many types of changes in the chromosomes, they are now known to contribute a very small fraction to the onset of obesity; knowledge of those changes might not have any direct effect on the treatment of obesity. However, if struggles with weight started in the first few years of life, there might be an indication to look for genes that are known to cause these syndromes. Your doctor will know to look for other symptoms that coexist with obesity, and he or she will order the appropriate test.

Can I Run into Problems with My Health Insurance Company If It Finds Out That I Am Predisposed to Obesity or Have Obesity?

In most cases, obesity will not affect your health insurance status. The Genetic Information Non-discrimination Act of 2008 prohibits health insurers from discrimination based on knowledge of genetic information. It states that health insurers may not use genetic information to make eligibility, coverage, underwriting, or premium- setting decisions. Typically, if an individual is struggling with weight control, doing the test and getting a positive genetic test does not change any insurance coverage or premiums, as the genetic test just provided an explanation for the problem. For example, a diagnosis of Prader-Willi syndrome would clarify the reasons for obesity and accompanying behavioral issues.

However, genetic testing for asymptomatic patients or their relatives can have implications for long-term disability insurance, life insurance, and other medical insurances later in life. In such cases, we counsel families to think about these matters before deciding on testing. This typically applies to a family member whose mother or father has a genetic condition (e.g., leptin deficiency), and they want to know whether they might also have it. In that case, if they tested positive, there could be some insurance issues.

Where Can I Get More Information About Being at Risk for Obesity?

The best place to start is with your doctor. He or she can give you information about the likelihood of your genetic risk of obesity. The internet is filled with information, but it is difficult to trust its reliability. There is no risk calculator currently available for the common form of obesity, but if you would like to read more about the genetics of obesity, the following websites can be helpful:

  • Pubmed: https://www.ncbi.nlm.nih.gov/
  • Omim: https://www.omim.org/
  • Obesity—medline; https://medlineplus.gov/
  • The Obesity Society: https://www.obesity.org/
  • Obesity Action Coalition: https://www.obesityaction.org/

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