Postmenopausal white women with genetic risk regain weight two times faster

UNIVERSITY PARK, Pa. — In a new study of women in post-menopause, white women with higher genetic risk of obesity regained weight about two times faster than white women whose genetic risk was lower. Black women in the study regained weight at a similar rate, regardless of their genetic risk.

Harold Lee, assistant professor of biobehavioral health at Penn State, led the team of researchers who examined how genetics affected weight loss and regain over time. Women in the study were between 50 and 79 years old and had lost an average of four pounds following a low-fat diet.

The study was published in the journal Obesity.

“Obesity is stigmatized and often associated with laziness,” said Lee, first author of the study. “That is a stubborn myth. This study demonstrated one way that genetics influence a person’s ability to manage their weight — by affecting how quickly they regain pounds after moderate weight loss.”

How did genetics affect weight change?

The researchers analyzed data from the National Institutes of Health’s Women’s Health Initiative Dietary Modification trial, a subset study from the longitudinal project currently in its 35th year that was designed to examine the impact of diet on breast cancer. The team selected this dataset because it tracked information — including genetic data — for a large number of participants over multiple years.

During the first year of the Women’s Health Initiative Dietary Modification trial, 9,897 participants in post-menopause — 6,147 white women and 3,750 Black women — met with a dietician 18 times, and most participants on the low-fat diet lost around four pounds during this period. In the following years, women met with the dietician four times per year, and most regained the lost weight during this time.

The researchers of the current study divided participants who lost weight into two groups — those with and without high genetic risk for obesity.

Genetic risk for obesity was assessed using a polygenic risk score, a measurement of millions of different genes to estimate a person’s risk for a specific health condition. Polygenic risk scores leverage genetic datasets with many thousands of people, and each gene in the score is weighted based on how strongly it correlates with the health condition of interest, with higher scores representing greater risk.

In the current study, the researchers classified participants as having high genetic risk for obesity if their polygenic risk score was in the top 5% of all participants.

When the research team examined how genetic risk affected weight-loss maintenance, they found that white women with high genetic risk regained an average of two pounds per year, while white women without high genetic risk regained half that amount.

“Maintaining weight loss is very difficult, and most women regained weight,” Lee said. “Unexpectedly, white women with high genetic risk regained the weight much faster, which could make maintaining a healthy weight even more difficult.”

Can genetics be overcome?

During the study, the researchers initially examined whether increased genetic risk for obesity affected whether people lost weight. Lee said they were surprised to find that all participants were equally likely to lose weight, regardless of their genetic risk or race. This result was not included in the paper, which focused on weight regain. Still, Lee said, it may have implications for people’s health.

“The United States has experienced an obesity epidemic over the past several decades,” Lee said. “This was not due to changes in human genetics. What changed, rather, was the environment around us, which — among other problems, including neighborhoods designed for driving rather than walking — is now full of easy-to-eat, unhealthy but appealing food options that overwhelm reward systems in the brain.”

The environment around people has contributed to widespread obesity, and some people are more vulnerable because of their genetics, according to Lee. This is why weight loss by all women in the study, regardless of their genetic profile, gives Lee hope, he said.

“In this study, we saw a clear effect of genetic risk in how quickly women regained weight,” Lee said. “On the other hand, genetic risk did not influence weight loss. When the environment was changed enough — in this case through a low-fat diet and meetings with a dietician every two-to-three weeks — women seemed to overcome genetic risk, at least temporarily.”

With enough changes to the environment, healthy weight maintenance might be possible regardless of people’s genetic risk, Lee explained.

“We are starting to understand the deeply complex factors that influence weight loss amount and speed, as well as weight gain or regain amount and speed,” Lee said. “Genetics matter, but so do environmental changes.”

Race and understanding genetic risk

Though genetic risk influenced weight regain for white women, it did not predict how quickly Black women regained weight. Lee said that two factors likely explain why the polygenic risk score was useful only for white women.

First, the genetic datasets used to create polygenic risk scores commonly contain many more white participants than Black participants. As a result, the risk score used in this study accounts for 12% of obesity in white people but only 8% of obesity in Black people.

“Because fewer Black people were involved in the creation of the risk score, it does not represent them as accurately,” Lee explained, noting that many different factors in addition to genetics can contribute to weight outcomes.

Second, any effect of genetics was harder to observe in this dataset because it contained fewer Black women compared to white women, Lee said.

“The combination of smaller sample size and the lower accuracy of the risk score likely prevented us from detecting how genetic risk affected weight changes in Black women in post-menopause,” Lee said.

Genetics likely affect weight for Black individuals, too, according to Lee, but until minoritized populations are better represented in data, researchers will not be able to detect those effects.

“This is a significant problem,” Lee said. “Researchers want to use genetic data to understand health and make recommendations for all people. We do not want to exclude subsets of people based on race. We need to find ways to include more people of color in large scale genetic studies.”

Christy Avery, Misa Graff, Daeeun Kim and Kari North of the Department of Epidemiology at University of North Carolina at Chapel Hill; Josh Arias of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute; Linda Van Horn of the Department of the Feinberg School of Medicine at Northwestern University; and Charles Kooperberg of The Division of Public Health Sciences at Fred Hutchinson Cancer Center contributed to this research.

This research was funded by the National Institutes of Health’s National Heart, Lung, and Blood Institute.

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