The researchers recommended caution to doctors basing medical advice on genetic risk data, and to consumers using genetic tests for predicting weight.
The study, “Polygenic Risk, Fitness, and Obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study,” was published in the journal JAMA Cardiology.
Despite suggestions that genetics is a large determinant of obesity, genome-wide association studies (GWAS) indicate that genetic risk is responsible for less than 4% of the variance in a person’s BMI — a measure of weight and height.
Recent studies had indicated that polygenic risk scores (PRS) — a composite measure that incorporates genetic variants across the human genome — may be used in the clinic to accurately predict the likelihood of becoming obese or overweight.
But scientists at Michigan Medicine Frankel Cardiovascular Center and the Cardiovascular Research Center at Massachusetts General Hospital instead propose that a person’s BMI in early adulthood is a far better predictor of future weight than genetics.
“We wanted to understand how, if at all, genetic data would add to the information already routinely available in clinic. It turns out, our standard clinical exam, including an assessment of BMI, actually has vastly more information to help guide patient care,” Venkatesh Murthy, MD, PhD, a cardiologist at the Frankel CVC and the study’s lead author, said in a news story.
The researchers used results from the CARDIA study — Coronary Artery Risk Development in Young Adults — an assessment of more than 2,500 young adults across the U.S., sponsored by the National Institutes of Health. Data from 1,608 white individuals and 909 black individuals were collected between 1985 and 2011. Participants were followed-up for up to 25 years.
By comparing PRS and clinical measurements — including level of fitness, physical activity, and BMI — in early adulthood and 25 years later, researchers determined which of these factors best predicts being overweight and obesity later on.
The results revealed that — when combined with age, sex, and parental history of being overweight — BMI during young adulthood accounted for 52.3% of one’s BMI 25 years later.
If a person’s BMI was monitored over time, instead of just during young adulthood and then 25 years later, the prediction was even sharper and could explain up to 80% of BMI variation in midlife.
In contrast, polygenic risk scores — also combined with age, sex, and parental weight history — could only explain 13.6% of the participants’ future BMI.
Adding cardiorespiratory fitness reports, assessed using treadmill exercises, to the prediction slightly increased its accounting to 18.1%.
“Comprehensive clinical risk profiles (incorporating BMI, its change over time, and behavioral factors), but not polygenic risk scores, offer substantial predictive ability for future BMI in the context of obesity prevention,” the investigators said.
Physical activity and self-reported family history of being overweight also had a similar degree of association with BMI. This suggests that fitness and activity early in life may counteract the consequences of a genetic risk for high BMI.
“Caution should be exercised in the widespread use of polygenic risk for obesity prevention in adults, and close clinical surveillance and fitness may have prime roles in limiting the adverse consequences of elevated BMI on health,” the team added.
PRS was more effective at predicting long-term BMI trends in white individuals than in black individuals, the results showed. Genetic risk profiles are built primarily from data culled from European populations, so caution should be taken when applying these scores to non-white patients, the scientists said.
Murthy also called for prudence about the use of available genetic tests, which are gaining a rising interest. While the utility of these tests is unclear, they may lead people to change their behavior — and not always in a good way.
“We don’t know those answers very well yet,” Murthy said. “However, some data says, whether based on a real genetic score or not, people may perform better in fitness tests if they’re told they’re genetically more likely to be fit. And we run a risk of demotivating some people if we tell them the genetics are against them, even though we now know other associations with BMI are stronger than genetics.”
While genetic risk may be most important for rare cases of genetic obesity, “for the majority of the population at risk for becoming obese, universal recommendations like healthy eating and remaining active are important and should be reviewed regularly with your personal physician,” said Ravi Shah, MD, an assistant professor of medicine at Massachusetts General Hospital and the study’s senior author.