Gene Linked to Obesity Hasn’t Always Been a Problem, Study Finds

Among scientists who study how our DNA affects our weight, a gene called FTO stands out. “It’s the poster child for the genetics of obesity,” said Struan F. Grant, an associate professor of pediatrics at the University of Pennsylvania School of Medicine.

In 2007, researchers discovered that people with a common variant of FTO tend to be heavier than those without it. Since then, studies have repeatedly confirmed the link. On average, one copy of the risky variant adds up to 3.5 extra pounds of weight. Two copies of the gene bring 7 extra pounds — and increase a person’s risk of becoming obese by 50 percent.

But the gene doesn’t seem to have always been a problem. If scientists had studied FTO just a few decades ago, they would have found no link to weight whatsoever. A new study shows that FTO became a risk only in people born after World War II.

The research, published this week in the Proceedings of the National Academy of Sciences, raises questions that extend far beyond obesity. Genes clearly influence our health in many ways, but so does our environment; often, it is the interplay between them that makes the difference in whether we develop obesity or cancer or another ailment.

But the relative importance of certain genes may shift over the years, the new study suggests, as our environment changes.

James Niels Rosenquist of Massachusetts General Hospital and his colleagues were inspired to conduct the study by recent research documenting how people’s experiences alter the effects of their genes. A variant of a gene called AKT1, for example, can raise the risk of psychosis — but only if the carrier smokes a lot of marijuana. If he avoids smoking, the AKT1 variant doesn’t cause a problem.

To document genetic links to disease, scientists have compared people only at a single moment in history, Dr. Rosenquist noted. “They weren’t thinking in the dimension of time, because they didn’t have the data for it,” he said.

Yet our environment has changed drastically over the past century. We eat different kinds of food today, we have different jobs, and we use different chemicals and technology. Dr. Rosenquist and his colleagues wondered if our genes have had different influences on health at different times in history.

The scientists decided to focus on FTO, because its effects are so clear. To reconstruct its history, they took advantage of a remarkable study that has been running for over 60 years.

In 1948, researchers enlisted over 5,000 people in Framingham, Mass., and began to follow their health. In 1971, the so-called Framingham Heart Study also recruited many of the children of original subjects, and in 2002, the grandchildren joined in. In addition to such data as body mass index, the researchers have been gathering information on the genes of their subjects.

The scientists compared Framingham subjects with the risky variant of FTO to those with the healthy variant. Over all, the scientists confirmed the longstanding finding that people with the risky FTO variant got heavier.

But when they compared subjects born in different eras, the data told a surprising story.

People born before the early 1940s were not at additional risk of putting on weight if they had the risky variant of FTO. Only subjects born in later years had a greater risk. And the more recently they were born, the scientists found, the greater the gene’s effect.

Some change in the way people lived in the late 20th century may have transformed FTO into a gene with a big impact on the risk of obesity, the researchers theorized. Giles S.H. Yeo, a geneticist at the University of Cambridge who wasn’t involved in the study, said he suspected that physical activity had something to do with the change.

It is possible that before World War II, people were so physically active that they were shielded from FTO’s obesity risks. As people became sedentary, they lost that protection and the gene emerged as a danger.

Timothy M. Frayling, a geneticist at the University of Exeter Medical School who was not involved in the study, suspects that modern diets also may have increased FTO’s impact.

He points to recent studies that find that FTO increases appetite. Dr. Frayling also notes that people who eat fried foods or drink sugary beverages gain more weight if they have the FTO variant, compared to those who do not.

“You could imagine any gene that affects appetite would have a bigger effect in today’s environment, where we all have lots of access to food,” Dr. Frayling said.

While Dr. Frayling said he thought the new study made sense, he cautioned that it needed to be replicated in bigger groups of people — a difficult task.

Dr. Nicholas A. Christakis, a sociologist and physician at Yale University and a co-author of the new study, suggested that the influence of many other genes on health had waxed and waned over the past century. Reconstructing this history could drastically influence the way doctors predict disease risk. What might look like a safe version of a gene today could someday become a risk factor.

“The thing we think is fixed may not be fixed at all,” said Dr. Christakis.