Abstract
Background:Previous studies reporting on the interaction between physical activity and genetic susceptibility on obesity have been cross-sectional and have not considered the potential influences of other lifestyle behaviours. The aim of this study was to examine modification of genetic influences on changes across age in adiposity during mid-adulthood by physical activity and smoking.Methods:The sample comprised 2444 participants who were genotyped for 11 obesity variants and had body mass index (BMI), waist circumference-to-height ratio (WHtR), physical activity and smoking measures at 36, 43, 53 and 60–64 years of age. A genetic risk score (GRS) comprising the sum of risk alleles was computed. Structural equation models investigated modification of the longitudinal GRS associations by physical activity (active versus inactive) and smoking (non-smoker versus smoker), using a latent linear spline to summarise BMI or WHtR (multiplied by 100) at the age of 36 years and their subsequent rates of change over age.Results:Physical activity at the age of 36 years attenuated the GRS associations with BMI and WHtR at the same age (P-interaction 0.009 and 0.004, respectively). Further, physical activity at the age of 53 years attenuated the GRS association with rate of change in BMI between 53 and 63 years of age (by 0.012 kg m−2 per year (95% confidence interval (CI): 0.001, 0.024), P-interaction 0.004). Conversely, smoking at the age of 43 years showed a trend towards augmenting the GRS association with rate of change in WHtR between 43 and 63 years of age (by 0.012 (95% CI: 0.001, 0.026), P-interaction 0.07). Estimated GRS effect sizes were lowest at all ages in the healthiest group (e.g., active non-smokers).Conclusions:Healthy lifestyle behaviours appeared to attenuate the genetic influence on changes across age in BMI and central adiposity during mid-adulthood. An active lifestyle and not smoking may have additive effects on reducing the genetic susceptibility to obesity in adults.
Highlights
Genome-wide association studies have identified common genetic variants robustly associated with anthropometric indicators of adiposity.[1,2,3,4,5,6,7] To date, there are 32 well-established genetic loci for body mass index (BMI) in middle-aged adults of European descent,[1,2,4,5,6] and the strongest loci for BMI are the same as those for indictors of central adiposity such as waist circumference.[3]
The SEMs for BMI were re-run using the weighted genetic risk score (GRS) to confirm that constraining each single-nucleotide polymorphisms (SNPs) to have an equal contribution to genetic risk in the main analyses was not inappropriate. Both BMI and waist circumference-to-height ratio (WHtR) increased across adulthood so that by 60–64 years of age 72% of the sample was overweight or obese and 86% had central obesity (Table 1)
The GRS was positively associated with BMI and WHtR Z-scores at all ages
Summary
Genome-wide association studies have identified common genetic variants robustly associated with anthropometric indicators of adiposity.[1,2,3,4,5,6,7] To date, there are 32 well-established genetic loci for body mass index (BMI) in middle-aged adults of European descent,[1,2,4,5,6] and the strongest loci for BMI are the same as those for indictors of central adiposity such as waist circumference.[3]. The pertinent public health question is whether or not an individual can attenuate the influence of their genetic risk for adiposity by healthy lifestyle behaviours? The aim of this study was to examine modification of genetic influences on changes across age in adiposity during mid-adulthood by physical activity and smoking. Structural equation models investigated modification of the longitudinal GRS associations by physical activity (active versus inactive) and smoking (non-smoker versus smoker), using a latent linear spline to summarise BMI or WHtR (multiplied by 100) at the age of 36 years and their subsequent rates of change over age. CONCLUSIONS: Healthy lifestyle behaviours appeared to attenuate the genetic influence on changes across age in BMI and central adiposity during mid-adulthood. An active lifestyle and not smoking may have additive effects on reducing the genetic susceptibility to obesity in adults
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