Are Genes a Reason for Obesity and Other Ills—Or Just an Excuse?

Two in three Americans are overweight, of whom half are obese. The trend is worsening worldwide; so much so, that it’s estimated that by 2030 the number of people in the world with diabetes will be closing in on half a billion.

Some people look at their expanding waistline and blame their genes. When they subsequently come down with serious medical conditions that are likely obesity-related, again, they are likely to insist it just runs in their family.

Are they right? Is their gene pool more of a cesspool? Or are they just making excuses? There has long been interest in understanding the impact of genes and environment when it comes to apportioning responsibility for obesity. One of the leaders in this field is Paul Franks, MD.

You Must Remember This

Forgive the basic science reminder, but a little of it is necessary to tell the story.

As Dr. Franks explains, the genome is the conduit through which the environment conveys many of its effects on the phenotypes involved in health and disease. There are a lot of environmental influences to our health or lack thereof. Common environmental triggers include smoking, exercise, diet, infection, stress, heat, cold, drugs, and toxins.

Disruption of the signaling circuit in our genetic machinery occurs in the form of DNA variants that impact the cellular environment. This concept is broadly referred to as the gene-environment interaction (or genotype-environment interaction, or GEI). In this G×E equation, the "gene" is usually one or more DNA variants and the "environment" can be any nongenetic factor that impacts risk.

Importantly, the intersection of genes and environment should not be considered one-way streets. Affecting the cellular machinery can either enhance the effects of unhealthy environmental exposures or protect against development of disease.

Living in Those Old Genes

In animal, plant, and bacterial genetics, numerous examples of GEI exist. There are also many tangible examples of GEI in humans. Carrying a change in the FTO gene is common (found in three-quarters of Europeans and North Americans) and is associated with a 20-30% increased risk of obesity. In a recent paper, Dr. Franks and colleagues noted that some overweight or obese individuals may feel that the dice are loaded and there is little point in fighting the fat.1 Indeed, warning people that they have a genetic susceptibility to obesity may not help; especially if their response is to throw up their hand and still end up choosing a poor diet.

A similar fatalism may occur when overweight and obese people consider physical activity. But disentangling the influence of physical activity on those genetically susceptible to obesity from other factors that might impact weight is not straightforward, as it requires large sample sizes, could be subject to publication bias, and may rely on less than ideal self-reporting methods.

To determine the effect of physical activity on the FTO gene and obesity risk, Dr. Franks and more than 100 other investigators conducted a meta-analysis of data from 45 studies of adults (n  =  218,166) and nine studies of children and adolescents (n  =  19,268). While the effect was not seen in younger people, physical activity actually attenuated the FTO gene effect in adults, highlighting the importance of physical activity—particularly in those genetically predisposed to obesity.

So, the deterministic view seems to be wrong: we are not the victims of our genes. This was apparent in a 1990 paper by Claude Bouchard, PhD, and colleagues who reported on the long-term response to overfeeding in 12 sets of identical male twins.2 There were sizable differences reported with respect to changes in body weight and body composition with nearly 3 months of identical overfeeding. Although the mean increase in body weight was 8.1 kg, the range was 4.3 to 13.3 kg (9.5-29.3 pounds). Differences within a single pair of twins were not as broad as those seen across the twin participants, but even between identical twins there were notable differences.

In brief, a comparable surplus intake of energy over a relatively long period of time did not cause identical responses with respect to body mass, body composition, or regional fat distribution in these sedentary young men. The results strongly support the view that there are individual differences in the tendency toward obesity and in the distribution of body fat. The findings suggest that these differences are partly related to undetermined genetic characteristics.

According to Dr. Franks, the evidence demonstrates that people vary genetically in their susceptibility to the effects of environmental risk factors for many diseases. Genetic variation also underlies the extent to which people respond appropriately to clinical therapies. Defining the basis to the interactions between the genome and the environment may help elucidate the biologic basis to diseases such as type 2 diabetes (which Dr. Franks covers well in his Current Diabetes Reports paper), as well as help target preventive therapies and treatments.3

Currently, Dr. Franks is recruiting post-docs to work on a very large European project with an "outstanding team in a world-class research environment." He can be contacted by e-mail:


  1. Kilpeläinen TO, et al. PLoS Med. 2011;8:e1001116.
  2. Bouchard C, et al. N Engl J Med. 1990;322:1477-82.
  3. Franks PW. Curr Diab Rep. 2011;11:552-61.


    To listen to an interview with Paul Franks, MD, about obesity and the gene-environment interaction, visit The interview was conducted by Robert A. Vogel, MD.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Prevention, CHD & Pediatrics and Prevention, CHD & Pediatrics and Quality Improvement, Diet, Smoking

Keywords: Genetic Variation, DNA, Overweight, Environmental Exposure, Diabetes Mellitus, Type 2, Individuality, Gene Pool, Risk Factors, Publication Bias, Smoking, Child, Twins, Monozygotic, Body Composition, Genetic Predisposition to Disease, Motor Activity, Electronic Mail, Gene-Environment Interaction, Obesity, Diet, United States, Hot Temperature

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