Adherence to healthy diets can overrule genetic predisposition for obesity

Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies

Literature - Wang T, Heianza Y, Sun D, et al. - BMJ 2018;360:j5644


The Alternate Healthy Eating Index 2010 (AHEI-2010), the Dietary Approach to Stop Hypertension (DASH), and the Alternate Mediterranean Diet (AMED) scores have been associated with a lower risk of chronic disease [1-5]. The interactions between changes in adherence to healthy dietary patterns over time and the genetic susceptibility to obesity on long term weight gain have not been studied.

This study examined whether changes in the AHEI-2010, DASH, and AMED scores interact with a genetic predisposition to obesity as evaluated by a genetic risk score based on 77 genetic variants known to be associated with BMI. Long term changes in BMI and body weight for up to 20 years were monitored in 2 independent, prospective cohorts: the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). This analysis included 8828 women and 5218 men of European ancestry who had complete baseline information and available genotype data based on genome-wide association studies, and were free from diabetes, cancer, or CVD at baseline. Weight and BMI were assessed every four years.

Main results

  • Overall, the mean genetic risk score (69.5; SD: 5.5 in NHS and 69.3; SD: 5.6 in HPFS) correlated significantly with BMI andt with increases in body weight.
  • The difference in BMI change between people at high vs. low genetic risk was more prominent in persons with lower adherence to the AHEI and DASH, but not AMED diets.
  • When all diets were considered together, genetic associations with BMI changes were weaker in those with higher adherence to the AHEI and DASH diets. Conversely, those at high genetic risk showed the strongest adverse association of better diet adherence and change in BMI. Associations of genetic score with change in BMI were weaker if AHEI diet score was higher. The BMI change associated with a 10 risk allele increment in the lowest third with decreased AHEI score corresponded to a weight change of 0.16 kg vs. -0.02 kg in the third with increased AHEI score. DASH scores showed a similar pattern, while AMED did not.
  • Increase in diet quality scores over time were associated with decreases in BMI and body weight, and this association was more prominent in those with higher genetic risk.
  • Increases in AHEI and DASH scores attenuated the genetic association with change in BMI, while the AMED diet did not show a significant interaction.
  • When considering individual dietary components, significant interactions between intake of fruits, vegetables, long chain n-3 fats or trans fat and the effect of genetic risk score on change in BMI or body weight were noted.


This study showed that improving adherence to healthy dietary patterns can attenuate the effect of genetic predisposition to long-term changes in BMI and weight increases, particularly in individuals at high genetic risk. Thus, especially in people genetically predisposed to obesity improving adherence to a healthy diet is important and beneficial for weight management.

Editorial comment

In their editorial article [6], Ells et al. discuss the limitations of the Wang et al. study, which include unmeasured confounders, like physical activity, the non-randomized adherence to healthy diet, a possible reverse causality, the lack of generalizability and clear underlying biological plausibility, and the small effect size of the genetic predisposition. Moreover, they highlight the challenges of eating healthy in environments that promote obesity, and they conclude: ‘Genetic predisposition is no barrier to successful weight management and no excuse for weak health and policy responses. Through evidence based and cost effective interventions at both individual and societal levels, governments and populations must act to ensure universal healthy diets within health promoting food environments and food systems. This must become the new normal. Only then will we begin to curb and ultimately reverse the global epidemic of obesity.’

Find this article online at BMJ

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