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April 22, 2019

Is obesity in your genes? New test offers clues.

Daily Briefing

    Researchers have developed a new test that can determine whether someone has genetic variants that place them at a greater risk of becoming overweight, according to a study published in the journal Cell on Thursday.

    Genetic testing—and 7 other technologies that could transform health care

    The study is the latest in a wave of so-called polygenic risk scores that aim to determine how various genetic variants affect a person's risk of developing various conditions from diabetes to experiencing a heart attack, and now of becoming obese.

    Predicting obesity in adults and children

    For the study, a group of Harvard-affiliated researchers sought to determine if they could create a polygenic risk score for obesity. They noted, "Obesity is known to be heritable and highly polygenic." They added, "[T]he majority of inherited susceptibility is related to the cumulative effect of many common DNA variants."

    The researchers used computer algorithms to analyze a list of 2.1 million common genetic variants to come up with possible scores that gauged the variants' obesity risk.  To find the "best" or most "effective" score, the researchers tested the accuracy of each at predicting BMI against data from 119,951 participants from the United Kingdom's Biobank.

    Once the researchers found the best polygenic predictor, they tested the predictor's ability to predict the BMI, weight, and severe obesity of more than 300,000 individuals whose age ranged from birth to 69. The mean age of the participants was 57 years and the mean BMI was 27.4. According to the study, 23.9% of participants were obese and 1.8% were severely obese.

    The researchers' polygenic risk score determined that the 10% of adults who, based on their genetic determinants, were most likely to be obese were 29 pounds heavier on average and 25 times more likely to become severely obese than the 10% of participants whose genes showed that they were likely to stay thin.

    "What this really means is 10% of the population has inherited a genetic factor that makes them 20-30 pounds heavier," Sekar Kathiresan, a cardiologist at Massachusetts General Hospital and leader of the study, said.

    But, the results also showed that genetics are not the sole determinant of a person's weight or BMI. Of the participants who were at the highest risk of being obese, 17% had a normal weight. According to Kathiresan, genetic variants were responsible for less than 25% of the heritability of BMI.


    Kathiresan said the study suggests there may be an effective way to screen children between birth and age 8—what he deemed the "golden period" of early childhood—for obesity risk. However, he noted that before the score could be used in such a manner, clinicians would first need to determine if there are appropriate interventions for children found to be at a high genetic risk of obesity.

    However, other experts are skeptical of polygenic risk scores for obesity because it's commonly believed one's environment plays an almost equal role as genes.

    Ruth Loos, a genetic epidemiologist and professor at the Icahn School of Medicine at Mount Sinai, said, "If you have a score that only represents 10% of the overall obesity susceptibility, you can never accurately predict future obesity" (Robbins, STAT News, 4/18; Kolata, New York Times, 4/18).

    Genetic testing—and 7 other technologies that could transform health care

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