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

By Mohamed Abdulkadir, Christopher Hübel, Moritz Herle, Ruth J.F. Loos, Gerome Breen, Cynthia Bulik, Nadia Micali

Posted 16 Oct 2020
medRxiv DOI: 10.1101/2020.10.15.20200600

BackgroundDeviating 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. MethodsAN-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. ResultsBetween 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. ConclusionAN-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.

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