Obesity and Genetics


Obesity results when body fat accumulates over time as a result of a chronic energy imbalance (calories consumed exceed calories expended). Obesity is a major health hazard worldwide and is associated with several relatively common diseases such as diabetes, hypertension, heart disease, and some cancers.

See also Obesity and Weight Loss.

The “obesity epidemic” – can genes really be involved?

In recent decades, obesity has reached epidemic proportions in populations whose environments offer an abundance of calorie-rich foods and few opportunities for physical activity. Although changes in the genetic makeup of populations occur too slowly to be responsible for this rapid rise in obesity, genes do play a role in the development of obesity. Most likely, genes regulate how our bodies capture, store, and release energy from food. The origin of these genes, however, might not be recent.

How might genes contribute to obesity? A “thrifty genotype” hypothesis

Any explanation of the obesity epidemic has to include both the role of genetics as well as that of the environment. A commonly quoted genetic explanation for the rapid rise in obesity is the mismatch between today’s environment and "energy-thrifty genes" that multiplied in the past under different environmental conditions when food sources were rather unpredictable. In other words, according to the "thrifty genotype" hypothesis, the same genes that helped our ancestors survive occasional famines are now being challenged by environments in which food is plentiful year round.

What other ways might genes influence obesity?

It has been argued that the thrifty genotype is just part of a wider spectrum of ways in which genes can favor fat accumulation in a given environment. These ways include the drive to overeat (poor regulation of appetite and satiety); the tendency to be sedentary (physically inactive); a diminished ability to use dietary fats as fuel; and an enlarged, easily stimulated capacity to store body fat. Not all people living in industrialized countries with abundant food and reduced physical activity are or will become obese; nor will all obese people have the same body fat distribution or suffer the same health issues. This diversity occurs among groups of the same racial or ethnic background and even within families living in the same environment. The variation in how people respond to the same environmental conditions is an additional indication that genes play a role in the development of obesity. This is consistent with the theory that obesity results from genetic variation interacting with shifting environmental conditions.

 

What do we know about specific genes associated with obesity?

The indirect scientific evidence for a genetic basis for obesity comes from a variety of studies. Mostly, this evidence includes studies of resemblance and differences among family members, twins, and adoptees. Another source of evidence includes studies that have found some genes at higher frequencies among the obese (association studies). These investigations suggest that a sizable portion of the weight variation in adults is due to genetic factors. However, identifying these factors has been difficult.

Regarding the direct evidence for obesity genes, the best success stories come from several cases of extreme obesity due to mutations (changes in the genetic material) of single genes (monogenic cases). But those cases account for only a very small fraction of cases worldwide. More recently, however, mutations in a single gene (Melanocortin 4-receptor gene, related to the control of feeding behavior) have been found to be strongly associated with a minority (perhaps 5%) of obesity cases in several populations.

Progress in identifying the multiple genes associated with the most common form of obesity has been slow but is accelerating. As of October 2005 (the latest update of the Human Obesity Gene Map), single mutations in 11 genes were strongly implicated in 176 cases of obesity worldwide. Additionally, 50 chromosomal locations relevant to obesity have been mapped, with potential causal genes identified in most of those regions. (Chromosomes are threadlike structures that contain the genes densely packed into the nucleus of each cell.) Also, studies using genome-wide scans have focused on 253 groups of genes related to obesity, with about one-fifth of them reported by two or more studies. (Genome is the total number of genes contained in the chromosomes.) Finally, 426 variants of 127 genes have been associated with obesity. At least five independent studies have replicated each association in 22 of these genes.

Food Fight: The Inside Story of The Food Industry, America's Obesity Crisis, and What We Can Do About It

Obesity Before Birth: Maternal and prenatal influences on the offspring (Endocrine Updates)

Recently, several independent population-based studies report that a gene of unknown function (FTO, fat mass and obesity-associated gene) might be responsible for up to 22% of all cases of common obesity in the general population. Interestingly, this gene also shows a strong association with diabetes. The mechanism by which this gene operates is currently under intense scientific investigation.

How can public health genomics help reduce the impact of obesity in populations?

Scientists have made great advances in understanding important environmental causes of obesity as well as identifying several of the many genes that might be implicated. Major efforts are now directed toward assessing the interactions of genes and environment in the obesity epidemic. The translation of these efforts into public health practice, from a genomic point of view, will take time.

The Evolution of Obesity

Obesity and Genetics: What We Know, What We Don’t Know and What It Means

Introduction:  Rising rates of obesity seem to be a consequence of modern life, with access to large amounts of palatable, high calorie food and limited need for physical activity.  However, this environment of plenty affects different people in different ways.  Some are able to maintain a reasonable balance between energy input and energy expenditure.  Others have a chronic imbalance that favors energy input, which expresses itself as overweight and obesity.  What accounts for these differences between individuals?

What We Know:  What We Don’t Know:
Biological relatives tend to resemble each other in many ways, including body weight. Individuals with a family history of obesity may be predisposed to gain weight and interventions that prevent obesity are especially important. Why are biological relatives more similar in body weight?  What genes are associated with this observation?  Are the same genetic associations seen in every family?  How do these genes affect energy metabolism and regulation?
In an environment made constant for food intake and physical activity, individuals respond differently.  Some people store more energy as fat in an environment of excess; others lose less fat in an environment of scarcity.  The different responses are largely due to genetic variation between individuals.
 Why are interventions based on diet and exercise more effective for some people than others?  What are the biological differences between these high and low responders?  How do we use these insights to tailor interventions to specific needs?
Fat stores are regulated over long periods of time by complex systems that involve input and feedback from fatty tissues, the brain and endocrine glands like the pancreas and the thyroid.  Overweight and obesity can result from only a very small positive energy input imbalance over a long period of time.
 What elements of energy regulation feedback systems are different in individuals?  How do these differences affect energy metabolism and regulation?

Rarely, people have mutations in single genes that result in severe obesity that starts in infancy.  Studying these individuals is providing insight into the complex biological pathways that regulate the balance between energy input and energy expenditure.

 Do additional obesity syndromes exist that are caused by mutations in single genes?  If so, what are they?  What are the natural history, management strategy and outcome for affected individuals?
Obese individuals have genetic similarities that may shed light on the biological differences that predispose to gain weight.  This knowledge may be useful in preventing or treating obesity in predisposed people. How do genetic variations that are shared by obese people affect gene expression and function?  How do genetic variation and environmental factors interact to produce obesity?  What are the biological features associated with the tendency to gain weight?  What environmental factors are helpful in countering these tendencies? 
Pharmaceutical companies are using genetic approaches (pharmacogenomics) to develop new drug strategies to treat obesity.
 Will pharmacologic approaches benefit most people affected with obesity?  Will these drugs be accessible to most people? 
The tendency to store energy in the form of fat is believed to result from thousands of years of evolution in an environment characterized by tenuous food supplies.  In other words, those who could store energy in times of plenty, were more likely to survive periods of famine and to pass this tendency to their offspring.
 How can thousands of years of evolutionary pressure be countered?  Can specific factors in the modern environment (other than the obvious) be identified and controlled to more effectively counter these tendencies? 

What It Means

  1. For people who are genetically predisposed to gain weight, preventing obesity is the best course.  Predisposed persons may require individualized interventions and greater support to be successful in maintaining a healthy weight.
  2. Obesity is a chronic lifelong condition that is the result of an environment of caloric abundance and relative physical inactivity modulated by a susceptible genotype.  For those who are predisposed, preventing weight gain is the best course of action.
  3. Genes are not destiny.  Obesity can be prevented or can be managed in many cases with a combination of diet, physical activity, and medication.

 

How can family history help?

Fortunately, there is a simple way for public health genomics to start reducing the effects of obesity in populations. It is through the use of family history. Family history reflects genetic susceptibility and environmental exposures shared by close relatives. Health care practitioners can routinely collect family health history to help identify people at high risk of obesity-related disorders such as diabetes, cardiovascular diseases, and some forms of cancer. Weight loss or prevention of excessive weight gains is especially important in this high-risk group. Any health promotion effort to reduce the adverse impact of obesity in populations may be more effective if it directs more intensive lifestyle interventions to high-risk groups (high-risk prevention strategy). However, such strategies should not detract from the population prevention strategy, which recommends that regardless of genetic susceptibility and environmental exposure, all people should follow a healthful diet and incorporate regular physical activity into their daily routine to help reduce the risk of obesity and its associated conditions.

How can you tell if you or your family members are overweight?

Most health care practitioners use the Body Mass Index (BMI) to determine whether a person is overweight. Check your Body Mass Index with a BMI calculator.

Family Health History

Family members share genes, behaviors, lifestyles, and environments that together may influence their health and their risk of chronic disease. Most people have a family health history of some chronic diseases (e.g., cancer, coronary heart disease, and diabetes) and health conditions (e.g., high blood pressure and hypercholesterolemia). People who have a close family member with a chronic disease may have a higher risk of developing that disease than those without such a family member.

Family health history is a written or graphic record of the diseases and health conditions present in your family. A useful family health history shows three generations of your biological relatives, the age at diagnosis, and the age and cause of death of deceased family members. Family health history is a useful tool for understanding health risks and preventing disease in individuals and their close relatives.

Three Generation Degrees

  • First-degree = parents, brothers, sisters, children
  • Second-degree = aunts, uncles, nieces, nephews, grandparents, grandchildren
  • Third-degree = first cousins

Some people may know a lot about their family health history or only a little. It is helpful to talk with family members about your health history, write this information down, and update it from time to time. This way family members will have organized and accurate information ready to share with their health care provider. Family health history information may help health care providers determine which tests and screenings are recommended to help family members know their health risk. Anyone looking to find out more about their family history can perfrom amarriage records search, find obitutaries on past family members, or talk to some of the elder members of the family.

To help individuals collect and organize their family history information, CDC’s Office of Public Health Genomics collaborated with the U.S. Surgeon General and other federal agencies to develop a Web-based tool called My Family Health Portrait.

Q: What is family history?

A: Family history refers to health information about you and your close relatives. Family history is one of the most important risk factors for health problems like heart disease, stroke, diabetes and cancer. (A risk factor is anything that increases your chance of getting a disease.)

Family History in the Genes: Trace your DNA and grow your family tree

Q: Why is knowing my family history important?

A: Family members share their genes, as well as their environment, lifestyles and habits. A family history helps identify people at increased risk for disease because it reflects both a person’s genes and these other shared risk factors.

Q: My mother had breast cancer. Does this mean I will get cancer, too?

A: Having a family member with a disease suggests that you may have a higher chance of developing that disease than someone without a similar family history. It does not mean that you will definitely develop the disease. Genes are only one of many factors that contribute to disease. Other factors to consider include lifestyle habits, such as diet and physical activity.

If you are at risk for breast cancer, consider following national guidelines for a healthy diet and regular exercise. It is also important to talk with your physician about your risk and follow recommendations for screening tests (such as mammograms) that may help to detect disease early, when it is most treatable.

Q: Because both of my parents had heart disease, I know I have “bad” genes. Is there anything I can do to protect myself?

A: First of all, there are no “good” or “bad” genes. Most human diseases, especially common diseases such as heart disease, result from the interaction of genes with environmental and behavioral risk factors that can be changed. The best disease prevention strategy for anyone, especially for someone with a family history, includes reducing risky behaviors (such as smoking) and increasing healthy behaviors (such as regular exercise).

Q: How can knowing my family history help lower my risk of disease?

A: You can’t change your genes, but you can change behaviors that affect your health, such as smoking, inactivity and poor eating habits. People with a family history of chronic disease may have the most to gain from making lifestyle changes. In many cases, making these changes can reduce your risk of disease even if the disease runs in your family.

Another change you can make is to participate in screening tests, such as mammograms and colorectal cancer screening, for early detection of disease. People who have a family history of a chronic disease may benefit the most from screening tests that look for risk factors or early signs of disease. Finding disease early, before symptoms appear, can mean better health in the long run.

Trace Your Genes to Health: Use Your Family Tree to Guide Your Diet, Enhance Your Immune System and Overcome Chronic Disease

Q: How can I learn about my family history?

A: The best way to learn about your family history is to ask questions, talk at family gatherings, draw a family tree and record health information. If possible, look at death certificates and family medical records.

You can collect your family history by talking to your relatives. Start with your parents if they are living. Older relatives are often good sources of information. Some relatives may not want to share their medical histories or they may not know their family history. However, whatever information you discover will be helpful. Vacations, holidays and family reunions can be good times to collect this information. As each generation ages, important information can be forgotten or lost – so now is the time to start your project! If you are adopted, you may be able to learn some of your family history through the parent(s) that adopted you or from adoption agency records.

Additional Sources of Information

Check whether your family has existing family trees, charts, listings of family members. Information may be recorded in baby books, birthday date books, or a family bible. Medical records are helpful but may be harder to obtain. There are offices in each state that have records of births, marriages and deaths. You can call the "County Clerk" office where you live (look in the "Government" section of the phone book) to find out how to get copies of these records. In addition, there are websites that have helpful resources for putting together family trees that you can find by searching for “genealogy.” It is important to collect accurate information, so verify the medical history whenever possible.

How to record your family history

One way to record a family history is by drawing a family tree called a “pedigree”. You can also create and keep a written list of this information without drawing a pedigree. Either way, begin by writing down the medical and health information on:

  • Yourself
  • Your brothers and sisters
  • Your children
  • Your parents

Then go back a generation at a time. Include:

  • Nieces and nephews
  • Aunts and uncles
  • Grandparents
  • Cousins

For each relative, try to write down as many of these items as possible:

  • Age or date of birth (and, for all family members who have passed on, age at death and cause of death). When the information is unavailable, write down your best guess (for example, “40’s”).
  • Medical problems such as:
    • Cancer
    • Heart disease
    • Diabetes
    • Asthma
    • Mental illness
    • High blood pressure
    • Stroke
    • Kidney disease
    • Alcoholism
    • Others
      Note the ages at which the conditions occurred. Did Uncle Pete have his heart attack at age 42 or age 88? Did your mother develop diabetes in childhood or as an adult?
    • Birth defects such as spina bifida, cleft lip, heart defects, others.
    • Learning problems, mental retardation.
    • Vision loss/hearing loss at a young age (remember to record the age it began).
    • For family members with known medical problems, jot down if they smoked, their diet and exercise habits, and if they were overweight. (for example, you could note that your brother John, who had a heart attack at age 40, weighs 300 lbs and smokes 2 packs a day).

After you draw your family tree, above your mother’s side of the family tree write down where her family members came from (for example, England, Germany, Africa etc.); then do the same for your father’s side of the family. This information can be helpful because some genetic health problems occur more often in specific ethnic groups. What to do after you have completed your family tree

You should keep your family tree in a safe place and update it every couple of years (or update it at a regular family gathering, such as Thanksgiving). You can share a copy with your doctor, who may find it helpful in caring for your health. If you have concerns about your family history, you may wish to see a genetic counselor. To find genetic counselors in your area, contact the National Society of Genetic Counselors; or the American Society of Human Genetics. To find more information about the medical conditions present in your family and about support groups, contact the Genetic Alliance.

Q: How do I learn about my family history if I'm adopted?

A: Learning about your family health history may be hard if you are adopted. Some adoption agencies collect medical information on birth relatives. This is becoming more common but is not routine. Laws concerning collection of information vary by state. Contact the health and social service agency in your state for information about how to access medical or legal records. The National Adoption Clearinghouse offers information on adoption and could be helpful if you decide to search for your birth parents.

Q: What should I do with the information?

A: First, write down the information you collect about your family history and share it with your doctor. Second, remember to keep your information updated and share it with your siblings and children. Third, pass it on to your children, so that they too will have a family history record.

Q: If I don’t have a family history of disease, does that mean I am not at risk?

A: Even if you don’t have a history of a particular health problem in your family, you could still be at risk. This is because you may be unaware of disease in some family members, or you could have family members who died young, before they had a chance to develop chronic conditions. Your risk of developing a chronic disease is also influenced by many other factors, including your habits and personal health history.

Q: Where can I find more information about family history?

A: The following Web sites provide additional information on family history:

Genetic Testing

Genetic tests have been developed for more than 2,200 diseases, of which about 2,000 are currently available for use in clinical settings. Most tests look at single genes and are used to diagnose rare genetic disorders, such as Fragile X Syndrome and Duchenne Muscular Dystrophy. In addition, some genetic tests look at rare inherited mutations of otherwise protective genes, such as BRCA1 and BRCA2, which are responsible for some hereditary breast and ovarian cancers. However, a growing number of tests are being developed to look at multiple genes that may increase or decrease a person’s risk of common diseases, such as cancer or diabetes. Such tests and other applications of genomic technologies have the potential to help prevent common disease and improve the health of individuals and populations. For example, predictive gene tests may be used to help determine the risk of developing common diseases, and pharmacogenetic tests may be used to help identify genetic variations that can influence a person’s response to medicines. There is much we still need to learn about how effective these new tests are, and the best way to use them to improve health.

Limited Scientific Information for Most Genetic Tests

Despite the many scientific advances in genetics, researchers have only identified a small fraction of the genetic component of most diseases. Therefore, genetic tests for many diseases are developed on the basis of limited scientific information and may not yet provide valid or useful results to individuals who are tested. However, many genetic tests are being marketed prematurely to the public through the Internet, TV, and other media. This may lead to the misuse of these tests and the potential for physical or psychological harms to the public. At the same time, valid and useful tests, such as those for hereditary breast and ovarian cancer or for Lynch syndrome, a form of hereditary colorectal cancer, are not widely used, in part because of limited research on how to get useful tests implemented into practice across U.S. communities. Individuals can learn more about specific genetic tests by visiting the Web sites listed below or by talking with their doctor.