Contributions of diet quality and genetic risk to weight change over the life course

Both dietary and genetic factors are known contributors to the development of overweight and obesity. Several studies have investigated their independent contributions as well as the interaction between these two factors. However, it is unclear whether associations of dietary and genetic factors with anthropometry vary over the life course.

Prior research has illustrated that a high quality diet is beneficially associated with body weight and overweight/obesity risk. Prospective cohort studies reported that better adherence to the Mediterranean Diet is associated with lower 2-year weight change,1 and lower 3-year obesity incidence in overweight adults.2 In addition, a meta-analysis of randomized controlled trials showed that Mediterranean Diet adherence positively contributes to intentional weight loss.3 With regard to genetics, previous studies showed that genetic risk scores comprised of risk-allele counts on multiple SNPs that were associated with BMI in genome-wide association studies, are also associated with long-term change in BMI4 and obesity risk5.

Although the relevance of both dietary and genetic factors in overweight development is clear, little is known about how associations hold over the life-course. In recent analyses within adult participants (aged 18-93) of the Lifelines cohort, an age-dependency of the association of diet quality (summarized in the Lifelines Diet Score6) and 4-year weight change was observed (Vinke et al., under review). In this study, it was illustrated that the association of poor diet quality with weight gain was strongest in young adults, aged 18-29, and decreased over decennial age categories towards a non-significant association in older age (age 60-69). In older women, aged 70 and over, the association was unexpectedly reversed, showing that poorer diet quality was associated with greater weight loss.

Also with regard to the association of genetic risk and body weight, an age-disparity may be present. In a study of 21.407 adults, a difference in the association of a genetic risk score of 31 BMI loci and weight change was found before and after middle age. Between age 20 and 58, annual weight change increased with a higher number of BMI-associated risk alleles. However, unexpectedly, from age 58 to 73, a higher number of BMI-associated risk alleles was associated with less weight gain. 7 Similar results were found in a study in 9.971 women and 6.405 men in whom BMI was measured repeatedly over the adult life course from age 18 to 80. In this study, higher genetic risk scores (based on 97 SNPs) were significantly associated with higher change in BMI in early adulthood (age 18-45). A weaker but still significant positive association was found in middle adulthood as well (age 45-65). In late adulthood (age 65-80), however, higher genetic risk scores were associated with greater weight loss. 8 These findings suggest that the life-course plays an important role in both the association of genetic and dietary factors with weight gain.

To our knowledge, the associations of dietary and genetic factors with weight gain have not yet been studied simultaneously. Investigating these associations simultaneously over the full adult life-course will provide valuable insights into when these exposures have their greatest effect, and may help to tailor overweight prevention strategies to age groups. Based on our previous work and literature described above, we hypothesize that for both dietary and genetic factors, strength of associations with weight change decreases over age categories (stratified per 10 years, from 18-29 to 60-69) and may be reversed in the elderly (70+).