Medical genetics

Scientists who recently announced an experimental genetic test that can help predict obesity got immediate pushback from other researchers, who wonder whether it is really useful. The story behind this back-and-forth is, at its core, a question of when it’s worth diving deep into DNA data banks when there’s no obvious way to put that information into use.

Help predict obesity

The basic facts are not in dispute. Human behavior and our obesity-promoting environment have led to a surge in this condition over the past few decades. Today about 40% of American adults are obese and even more are overweight. But genetics also plays an important role. People inherit genes that make them more or less likely to become seriously overweight.

While some diseases (like Huntington’s and Tay-Sachs) are caused by a single gene gone awry, that’s certainly not the case for common conditions, including obesity. Instead, thousands of genes apparently play a role in increasing obesity risk. Many of those gene variants contribute a minuscule risk.

Identify genetic patterns

Sekar Kathiresan, a cardiologist at Harvard and a geneticist at the Broad Institute, set out to see whether he and his team could find a bunch of these genetic variants and add up their effects. The goal was to identify genetic patterns that put people at the highest risk. This genetic information “could explain why somebody’s so big, why they have so much trouble keeping their weight down,” Kathiresan says.

His team identified more than 2 million DNA variants of potential interest. He figures most of those variants are irrelevant, but his hunch is, hidden somewhere in there are a few thousand changes that each contribute at least a tiny bit to a person’s risk of developing obesity.

No single gene can do much to move the needle. But he says the composite result, called a polygenic risk score, is still potentially useful. Those with the highest risk scores were more likely to be severely obese (with a body mass index over 40). In fact, 43% of the people with the highest genetic scores were obese.

Philosophical takeaway

But the score is far from perfect. For instance, 17% of the people with the highest scores had normal body weights. The team, with lead author Amit Khera, published its results in the journal Cell. “The impact of the genetics and this was a huge surprise to us as well starts very early in life, in the preschool years; around the age of 3,” Kathiresan says.
That finding suggests prevention efforts are more likely to succeed if they also start in childhood. Kathiresan has a more philosophical takeaway from his work as well. “I hope this work will hopefully destigmatize obesity and make it very similar to every other disease; which is a combination of both lifestyle and genetics.”