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Obesity Polygenic Risk Score Relatively Poor Predictor of Midlife BMI in Longitudinal Study

NEW YORK – Results from a new longitudinal population study suggest fitness levels may have as much or more to say about individuals' risk of carrying extra weight than do polygenic risk scores (PRS) based on SNPs previously implicated in obesity.

"Ultimately, while genetic risk may be most important in those individuals with rare inherited causes of 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," senior author Ravi Shah, a cardiology researcher at Massachusetts General Hospital, said in a statement.

With data collected for the Coronary Artery Risk Development in Young Adults (CARDIA) study, Shah and his colleagues followed more than 2,500 individuals recruited at centers in Alabama, Illinois, Minnesota, and California from the mid-1980s to 2011, looking at body mass index (BMI), fitness, activity levels, and more in relation to an obesity PRS.

The participants included 1,608 individuals of European ancestry and 909 individuals of African descent, genotyped using Affymetrix arrays and assessed over time for their height, weight, self-reported family history, fitness level, and other factors, the team explained in their paper, published online today in JAMA Cardiology.

By analyzing data collected from the participants over more than two decades, the investigators determined the obesity PRS — previously developed using data from Caucasian individuals — did have modest ties to individuals' weight at midlife, particularly in Caucasian participants.

In the white participants, for example, the team estimated that the risk score, in concert with age, family history, and other data, explained almost 14 percent of BMI variation at the individuals' midlife point, some 25 years after the study began.

Incorporating individuals' fitness data boosted BMI prediction slightly, the team found, and independently explained about as much BMI variation as the PRS itself. Likewise, it was possible to learn roughly as much about the participants' obesity risk by looking at other factors such as their activity levels or reports of obesity in their parents.

Perhaps most striking, the team determined that an individual's BMI in young adulthood held the greatest potential for predicting BMI later in life. Individual's baseline BMI — their weight when starting the study — explained more than half of their BMI variation at midlife, according to the analysis.

"We wanted to understand how, if at all, genetic data would add to the information already routinely available in clinic," first author Venkatesh Murthy, a cardiovascular medicine researcher at the University of Michigan, said in a statement. "It turns out, our standard clinical exam, including an assessment of BMI, actually has vastly more information to help guide patient care."

Based on these and other findings, the authors argued that "[ca]ution should be exercised in the widespread use of polygenic risk for obesity prevention in adults, and close clinical surveillance and fitness have prime roles in limiting the adverse consequences of elevated BMI on health."

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