Introduction & Objective: Early-life adversity contributes significantly to global disease burden but lacks objective measures. Given height is determined by genetic and early environmental factors, we aimed to assess early-life conditions by the difference between observed and genetically predicted height (i.e., residual height) and to examine its associations with risks of diabetes and related diseases.
Methods: Among 407366 UK Biobank participants, we calculated genetically predicted height by fitting age- and sex-specific linear regression models regressing observed height on a polygenic score of 9863 height-related SNPs (Fig A). Outcomes were obtained via disease registry (median follow-up=12.5 years).
Results: Residual height was correlated with favorable early-life indicators (Fig B). Shorter residual height (comparing <-2 SD to ≥2 SD away from the mean) was associated with higher risks of diabetes (HR 1.19, 95% CI 1.00-1.41), CVD (1.26, 1.10-1.45), psychiatric/neurological, digestive, musculoskeletal, and other diseases (HR range 1.13-1.25), and mortality (1.38, 1.23-1.55). Among 49 individual diseases, shorter residual height was associated with higher risks for 27 diseases (Fig C).
Conclusion: Shorter residual height, a potential early-life adversity indicator, was associated with higher risks of diabetes and related diseases.
Y. Zhang: None. Y. Li: None. X. Xue: None. T. Wang: None. J. Moon: None. C.R. Isasi: None. T. Rohan: None. Q. Qi: None.
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119268, R01DK120870, and R01DK126698), National Heart, Lung, and Blood Institute (R01HL060712), and National Institute on Aging (1RF1AG077639).
