Soler Family

Pursuing the Genetic Inheritance of Obesity and BMI

Obesity is a highly heritable condition. But in the general population, genes only explain about 40 to 50 percent of the variability in BMI. How can both of these things be true? Work to understand the causes of obesity spans a century. So scientists have learned a great deal about the genetic inheritance of obesity and BMI. Yet despite all that knowledge, much remains unknown.

For a short course on the genetics of obesity, the Obesity journal has just published an excellent review by Claude Bouchard. As you might expect from any good scholar, he raises as many questions as he answers.

Heritability Depends on the Population

The first thing to know is that heritability applies to a specific population. It’s an estimate of how much genes explain the variation in something across that population. In this case, the relevant characteristic is BMI. Its heritability depends upon the population at hand.

Thus, the heritability of BMI may be as low as 30 to 35 percent in individuals with a BMI in the range between 18.5 and 25. For them, other factors play a larger role in BMI than genes. But for people with obesity, genes explain 60 to 80 percent of the variation in BMI. So obesity is highly heritable condition. Yet, across the general population, genes play a moderate role in BMI and adiposity.

For people who like to argue the false dichotomy of nature versus nurture, this insight can be very disorienting. But the truth is that both environment and genes work together to produce obesity.

Which Genes Matter Most?

The next question is typically about the genes that cause obesity. Any number of entrepreneurs want to tap into the genetics of obesity to sell us something. Three years ago, 23andMe launched a clinical study to encourage folks to buy their genetic testing and see if it might help them lose weight. As a PR ploy, it was great. It generated lots of buzz and sales were good in 2018. As research, it hasn’t produced much yet. The “study” ended in 2019 and we can find no published results.

The truth is less satisfying than the buzz. Genomic screening tools for obesity are still very crude. So for practical purposes, they are not very useful yet. Bouchard explains:

“Recent progress in our understanding of the genetic predisposition to obesity has confirmed that such a vulnerability ranges from very low to very high. The obesity genetic risk is determined by hundreds and thousands of DNA variants, a fact that makes genetically based obesity prevention and treatment a major challenge.”

Progress?

Nonetheless, we have progress. We know of a handful of rare genetic defects can cause severe obesity. The recent approval of setmelanotide by FDA for treating three very specific defects shows that targeted therapies can be useful. This is an important advance, even though it helps only a small group of patients.

Knowledge about the genetic basis for BMI and obesity is bound to grow. With that knowledge will come new insights for treatment and prevention. Stay curious.

Click here for the Bouchard’s review.

Soler Family, painting by Pablo Picasso / WikiArt

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May x, 2021

4 Responses to “Pursuing the Genetic Inheritance of Obesity and BMI”

  1. May 03, 2021 at 8:43 pm, John Dixon said:

    It also important to reflect that environmental influences are transmitted to an infant from parents epigenetically, during foetal development, and very early life events including the development of child’s microbiome.

    The concept that we can choose non-heritable influences on BMI is deeply flawed.

  2. May 03, 2021 at 10:59 pm, Chester Draws said:

    100 years ago hardly anyone was obese.

    Our genes haven’t changed since then.

  3. May 04, 2021 at 4:14 am, Ted said:

    Chester, genes confer susceptibility. The environment acts upon that susceptibility, as I noted above. Through epigenetics, some of these environmental influences can be passed to subsequent generations. Bottom line, though our genes may not have changed much, the environment that activates our genetic susceptibility to obesity has changed. Thus, the prevalence of obesity has risen.

  4. May 04, 2021 at 8:07 pm, Michael Jones said:

    Since setmelanotide (Imcivree) hit the market about 2 months ago I’ve been able to start an 11yo female and a 9yo female (not related) on it for variants in POMC and PCSK1, respectively. Hopeful for good results.

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