The impact of anorexia nervosa and BMI polygenic risk on childhood growth: a 20-year longitudinal population-based study

Abstract

Background: Deviating growth from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGS) for AN and obesity are associated, individually or combined, with a range of anthropometric trajectories spanning the first two decades of life. Methods: AN-PGS and obesity-PGS were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; N= 8,654 participants with genotype data and at least one outcome measure). Using generalized (mixed) linear models, we associated PGS with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD). Growth trajectories were derived using spline modeling or mixed effects modeling. Results: Between age 5-24 years, Females with one SD higher AN-PGS had on average a 0.01% lower BMI trajectory, and between age 10-24 years a 0.01% lower FMI trajectory and 0.05% lower weight trajectory. Higher obesity-PGS was associated with higher BMI, FMI, LMI, BMD, weight, and lower height trajectories in both sexes. The average growth trajectories of females with high AN-PGS/low obesity-PGS remained consistently lower than those with low AN-PGS/low obesity-PGS; this difference did not reach statistical significance. However, post-hoc comparisons suggest that females with high AN-PGS/low obesity-PGS did follow lower growth trajectories compared to those with high PGS for both traits. Conclusion: AN-PGS and obesity-PGS have detectable sex-dependent effects on a range of anthropometry trajectories. These findings encourage further research in understanding how the AN-PGS and the obesity-PGS co-influence growth during childhood in which the obesity-PGS can mitigate the effects of the AN-PGS.

Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study

“…Additionally, we showed in the UK Biobank that the association between anorexia nervosa PRS and weight loss was not mediated through obesity genetics. One previous study examining the effect of anorexia nervosa PRS on early weight trajectory (from birth to age 24 years) 19 found a negative (albeit nonsignificant) association between anorexia nervosa PRS and weight change (per 1 SD higher anorexia nervosa PRS, weight was lowered by 0•63% in female individuals and 0•44% in male individuals, p≥0•13). Future studies that examine the causal effects of anorexia nervosa and obesity on a given weight trajectory would be of interest, using tools such as multivariable Mendelian randomisation.…”

“…[16][17][18] To our knowledge, only one previous study thus far has examined the association of the polygenic risk score (PRS) of anorexia nervosa with weight trajectory across childhood and young adulthood (ages 10-24 years), but they did not find an association between higher genetic risk for anorexia nervosa and weight loss trajectory. 19 Less is known about the association between the genetic risk for depression and weight trajectories.…”

Novel approaches to tackling emotional loss of control of eating across the weight spectrum

“…Also, a Mendelian randomisation analysis of people in the The Avon Longitudinal Study of Parents and Children (ALSPAC) longitudinal cohort found that a higher BMI at 7 years was later associated with binge eating (12) . Smaller studies also have shown a trajectory of overeating and higher weight precedes the emergence of binge spectrum disorders (13) whereas the opposite profile (leanness and weight suppression) precedes the development of anorexia nervosa (14,15) . In addition, a period of weight suppression increases odds for future onset of anorexia nervosa and bulimia nervosa, but not binge-eating disorder (16) .…”