Quantifying the impact of early life growth adversity on later life health.
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Goldman-Pham Raphael, Alter Matthew P, Bao Rebecca, Collins Sophie É, Debban Catherine L, Allinson James P, Ambler Antony, Bertoni Alain G, Caspi Avshalom, Lovinsky-Desir Stephanie, Ekstrom Magnus P, Engert James C, Jacobs David R, Malinsky Daniel, Manichaikul Ani, Michos Erin D, Moffitt Terrie E, Oelsner Elizabeth C, Ramrakha Sandhya, Rich Stephen S, Sack Coralynn, Stanojevic Sanja, Subbarao Padmaja, Sugden Karen, Theodore Reremoana, Watson Karol E, Williams Benjamin, Yang Bin, Dupuis Josée, Shaheen Seif O, Barr R Graham, Hancox Robert J, Smith Benjamin M
Аннотация
METHODS: Data were first analyzed from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4582; 56/43% female/male) and UKBiobank (n = 483,385; 54/46% female/male). Genotype-predicted height was calculated using a multi-ancestry polygenic height score. Height-GaP was calculated as the difference between measured and genotype-predicted adult height. Early-life growth conditions were ascertained prospectively via standardized procedures (ALSPAC) and mortality via death register (UKBiobank). Regression models examined: (i) adult height-GaP as the outcome with early-life growth conditions as predictors; and (ii) mortality as the outcome with adult height-GaP as predictor. All models were adjusted for age, sex, genotype-predicted height and genetic ancestry. Analyses were replicated in the Dunedin Multidisciplinary Health and Development Study (DMHDS; n = 855; 49/51% female/male) and the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6352; 52/48% female/male).
RESULTS: Here we show that among ALSPAC participants (median [IQR] age: 24 [18-25] years at height-GaP assessment), lower gestational age at birth, greater pre- and post-natal deprivation indices, tobacco smoke exposure and less breastfeeding are associated with larger adult height-GaP deficit (p < 0.01). Among UKBiobank participants (mean ± SD age: 56 ± 8 years at height-GaP assessment), height-GaP deficit is associated with death from all-causes (adjusted hazard ratio comparing highest-to-lowest height-GaP deficit quartile [aHR]: 1.25 95%CI: 1.21-1.29), atherosclerotic cardiovascular disease (aHR: 1.32 95%CI: 1.23-1.42) and coronary heart disease (aHR: 1.64 95%CI: 1.49-1.81). Early- and later-life height-GaP associations replicate in DMHDS and MESA.
CONCLUSIONS: This study introduces a precision index of early-life growth adversity deployable in adulthood to investigate the developmental origins of longevity and improve health equity across the life course.