A recent study published in the journal Cell Metabolism showed that changing lifestyle factors can offset genetic risk for obesity.
Obesity is a non-infectious pandemic caused by a sedentary lifestyle and excessive intake of energy-dense foods. Obesity is heritable and multifactorial. Several metabolic pathways contribute to weight gain and over 1,000 genetic variants are associated with obesity. It has commonly been thought that genetic predisposition to obesity cannot be modified.
However, studies on gene-environment interactions have suggested that some lifestyle factors may attenuate the effects of certain obesity-related genes. However, such studies were limited to a few obesogenic genes and lifestyle factors. Furthermore, it is unclear how modifiable lifestyle factors interact with genetic predisposition to obesity to reduce its burden.
Study: Associations between genetic risk, lifestyle and their interactions with obesity and obesity-related diseases. Image credit: Motiontion Films/Shutterstock
About the Research
In this study, researchers investigated whether modifiable lifestyle factors could offset genetic risk for obesity.They identified over 338,600 white British individuals from the UK Biobank who passed genetic quality controls, excluded over 1,000 subjects with missing data on body mass index (BMI) or obesity-related diseases (ORM), and included 337,554 individuals.
A polygenic score (PGS) was estimated based on genome-wide association studies of BMI in people of European descent. A healthy lifestyle score was calculated from five obesogenic lifestyle factors (alcohol intake, sleep duration, sedentary behavior, diet, and physical activity). The primary outcome was incident obesity, determined by analyzing health data from Biobank. Prevalent obesity was a secondary outcome and was defined as a baseline BMI ≥ 30 kg/m2.
Absolute risks were estimated by estimating odds ratios (ORs) and hazard ratios (HRs) for general and incident obesity by PGS percentile and lifestyle. HRs were estimated using Cox proportional hazards regression models, and ORs were assessed using logistic regression models. In addition, predicted probabilities of obesity by age 75 years were calculated. Incident ORMs were ascertained using hospital data, self-reporting, or death registry records.
Interactions between genetic risk and lifestyle for obesity were assessed using additive and multiplicative interaction analyses. Cox proportional hazards regression models examined the association of lifestyle and genetic risk with incident obesity and ORM. Associations of lifestyle categories, genetic risk categories, or both with general obesity were examined using multivariate logistic regression.
Graphical Abstract
Survey results
Obese people had higher PGS and fewer healthy lifestyle factors. Unhealthy lifestyle and high genetic risk were jointly and independently associated with obesity. The research team investigated the independent effect of genetic risk on obesity, adjusting for lifestyle group, and the independent effect of lifestyle on obesity, adjusting for genetic risk group.
Higher genetic risk was associated with increased risk of incident and prevalent obesity, regardless of lifestyle group. Similarly, poor lifestyles were associated with increased risk of incident and prevalent obesity, regardless of genetic risk. The HR for obesity for those with poor lifestyles and high genetic risk was 3.54 compared with those with a healthy lifestyle and low genetic risk.
Based on obesity incidence, the median probability of being obese by age 75 years was 2.8% in the unhealthy lifestyle group and 1.7% in the healthy lifestyle group. The corresponding estimates based on general obesity were 30.7% and 13.9%, respectively. Analysis of relative excess risk due to interactions between lifestyle and genetic risk revealed a clear additive interaction, and multiplicative interaction analysis gave consistent results.
Avoiding sedentary behavior was associated with the lowest odds of obesity, independent of genetic risk. Individuals with a healthy lifestyle and a high PGS had a similar risk of ORM to those with a low PGS. In contrast, individuals with an unhealthy lifestyle and a high PGS were at increased risk of ORM. After adjusting for BMI, the association between PGS and ORM risk was null.
Conclusion
In summary, adherence to a healthy lifestyle was associated with a reduced risk of obesity and related pathologies. The absolute difference in obesity risk between individuals with and without a healthy lifestyle increased as PGS increased. Modifiable lifestyle and genetic risk were jointly and independently associated with obesity.
Sedentary behavior is associated with a significantly increased risk of obesity, suggesting that avoiding sedentary behavior may be an effective strategy to combat obesity. Overall, adherence to a healthy lifestyle can significantly reduce the genetic predisposition to obesity. Therefore, a healthy lifestyle should be promoted regardless of genetic background.
