Abstract
Importance: Obesity is a major determinant of disease burden worldwide. Polygenic risk scores (PRSs) have been posited as key predictors of obesity. How a PRS can be translated to the clinical encounter (especially in the context of fitness, activity, and parental history of overweight) remains unclear. Objective: To quantify the relative importance of a PRS, fitness, activity, parental history of overweight, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) in young adulthood on BMI trends over 25 years. Design, Setting, and Participants: This population-based prospective cohort study at 4 US centers included white individuals and black individuals with assessments of polygenic risk of obesity, fitness, activity, and BMI in young adulthood (in their 20s) and up to 25 years of follow-up. Data collected between March 1985 and August 2011 were analyzed from April 25, 2019, to September 29, 2019. Main Outcomes and Measures: Body mass index at the initial visit and 25 years later. Results: This study evaluated an obesity PRS from a recently reported study of 1608 white individuals (848 women [52.7%]) and 909 black individuals (548 women [60.3%]) across the United States. At baseline (year 0), mean (SD) overall BMI was 24.2 (4.5), which increased to 29.6 (6.9) at year 25. Among white individuals, the PRS (combined with age, sex, self-reported parental history of overweight, and principal components of ancestry) explained 11.9% (at year 0) and 13.6% (at year 25) of variation in BMI. Although the addition of fitness increased the explanatory capability of the model (24.0% variance at baseline and up to 18.1% variance in BMI at year 25), baseline BMI in young adulthood was the strongest factor, explaining 52.3% of BMI in midlife in combination with age, sex, and self-reported parental history of overweight. Accordingly, models that included baseline BMI (especially BMI surveillance over time) were better in predicting BMI at year 25 compared with the PRS. In fully adjusted models, the effect sizes for fitness and the PRS on BMI were comparable in opposing directions. The added explanatory capacity of the PRS among black individuals was lower than among white individuals. Among white individuals, addition of baseline BMI and surveillance of BMI over time was associated with improved precision of predicted BMI at year 25 (mean error in predicted BMI 0 kg/m2 [95% CI,-11.4 to 11.4] to 0 kg/m2 [95% CI,-8.5 to 8.5] for baseline BMI and mean error 0 kg/m2 [95% CI,-5.3 to 5.3] for BMI surveillance). Conclusions and Relevance: Cardiorespiratory fitness in young adulthood and a PRS are modestly associated with midlife BMI, although future BMI is associated with BMI in young adulthood. Fitness has a comparable association with future BMI as does the PRS. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 263-271 |
| Number of pages | 9 |
| Journal | JAMA cardiology |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2020 |
Funding
Development in Young Adults (CARDIA) study is conducted and supported by the NHLBI in collaboration with The University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). reported receiving research grants and personal fees from Siemens Medical Imaging and Singulex; receiving speaking honoraria from Siemens Medical Imaging; receiving personal fees for expert witness testimony from Jubilant Draximage; serving on medical advisory boards for and receiving personal fees from Curium and Ionetix; owning stock options is Ionetix; and owning common stock in General Electric. Drs Murthy and R. V. Shah reported being supported by research grants from the National Institutes of Health (NIH). Dr Sidney reported receiving grants from the National Heart, Lung, and Blood Institute (NHLBI). Dr Sarzynski reported receiving research grants from the NIH and being a consultant for and receiving personal fees from Genetic Direction LLC. Dr Lima reported receiving grants from The Johns Hopkins University. Dr S. J. Shah reported receiving research grants from Actelion, AstraZeneca, Corvia, the NIH, and Novartis and reported receiving consulting fees from Abbott, Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Coridea, CVRx, Eisai, Ionis, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, Tenax, and United Therapeutics. Dr R. V. Shah reported serving as a consultant for Amgen, MyoKardia, and Best Doctors and being a coinventor on a patent for ex-RNA signatures of cardiac remodeling. No other disclosures were reported.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
