Common genetic variants associated with BMI in middle-aged people result in a higher risk for cardiovascular disease in people born after 1960

Common genetic variants associated with body mass index (BMI) in middle-aged people have larger effects and result in a higher risk for cardiovascular disease in people born after 1960, according to research from UTHealth Houston School of Public Health. 
 
The study, led by Chloé Sarnowski, PhD, assistant professor in the Department of Epidemiology, Human Genetics & Environmental Sciences, was published in the January 2023 edition of Circulation: Genomic and Precision Medicine.
 
“Given the current obesity epidemic in the U.S., it is crucial to understand whether an environment that promotes an energy balance where calorie intake is greater than the energy spent in activity, weight gain, and obesity amplifies or nullifies genetic effects, and whether modifying these environmental factors can reduce the impact of genetics on obesity and its downstream cardiovascular consequences,” Sarnowski said.
 
The researchers analyzed four birth cohorts spanning three generations of the Framingham Heart Study, starting from birth before 1932 and birth after 1960. Their work concluded that there was a larger effect of a higher genetic predisposition to obesity, as modeled by a genetic risk score, on BMI in people born more recently compared to almost a century ago. A person's DNA  is determined at birth, and a risk score can estimate an individual’s underlying genetic risk of developing a disease or propensity for a physical trait based on their genotype profile. By leveraging data from the Framingham Heart Study, this study suggested that the obesogenic environment – physical, economic, social, and cultural factors that promote obesity – may amplify the impact of genetics on the risk of obesity and its cardiovascular consequences. 
 
Each birth cohort studied was impacted by different historical events, such as World War I, the Great Depression, World War II, and the economic boom experienced postwar, accompanied by rapid technological advancement, modern transportation, and a calorie-dense Western diet, according to the researchers  This led Sarnowski and the co-authors to hypothesize that the effect of a higher genetic predisposition to obesity on BMI and potentially the risk of CVD may be larger in more recent years. 
 
The study results  suggest that if industrialized countries modify the environment to encourage physical activity, limit the availability of calorie-dense foods, and promote healthy living, “the impact of genetics on obesity risk and its downstream cardiovascular consequences could be reduced,” Sarnowski said.
 
This research collaboration between UTHealth Houston, Massachusetts General Hospital, Boston University, and the University of Washington, consisted of endocrinologists, cardiologists, biostatisticians, and statistical geneticists who analyzed, interpreted, and translated the findings to provide recommendations for obesity prevention and care.
 
“Our study supports recommendations that target, in addition to BMI, the entire complement of risk factors in cardiovascular disease prevention,” Sarnowski said.

Contributing authors for the paper included Matthew P. Conomos, PhD, University of Washington; Ramachandran S. Vasan, MD, Boston University School of Medicine; James B. Meigs, MD, Massachusetts General Hospital and Harvard Medical School; Josée Dupuis, PhD, Boston University School of Public Health; Ching-Ti Liu, PhD, Boston University School of Public Health; and Aaron Leong, MD, MSc, Massachusetts General Hospital and Harvard Medical School.