Quantifying the impact of early-life growth adversity on later-life health

Goldman-Pham, R., Alter, M. P., Bao, R., Collins, S. E., Debban, C. L., Allinson, J. P., Ambler, A., Bertoni, A. G., Caspi, A., Lovinsky-Desir, S., Ekstrom, M. P., Engert, J. C., Jacobs, D. R., Malinsky, D., Manichaikul, A., Michos, E. D., Moffitt, T. E., Oelsner, E. C., Ramrakha, S., Rich, S. S., Sack, C., Stanojevic, S., Subbarao, P., Sugden, K., Theodore, R., Watson, K. E., Williams, B., Yang, B., Dupuis, J., Shaheen, S. O., Barr, R. G., Hancox, R. J., Smith, B. M.

Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec Canada · medrxiv

Paper

Abstract

Background: Early-life growth adversity is important to later-life health, but precision assess-ment in adulthood is challenging. We evaluated whether the difference between attained and genotype-predicted adult height ("height-GaP") would associate with prospectively ascertained early-life growth adversity and later-life all-cause and cardiovascular mortality. Methods: Data were first analyzed from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UKBiobank. Genotype-predicted height was calculated using a multi-ancestry polygenic height score. Height-GaP was calculated as the difference between measured and gen-otype-predicted adult height. Early-life growth conditions were ascertained prospectively via standardized procedures (ALSPAC) and mortality via death register (UKBiobank). Regression models adjusted for age, sex, genotype-predicted height and genetic ancestry. Analyses were replicated in the Dunedin Multidisciplinary Health and Development Study (DMHDS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Findings: Among 4,582 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 were associated with larger adult height-GaP deficit (p<0.01). Among 483,385 UKBiobank participants (mean+-SD age: 56+-8 years at height-GaP assessment), height-GaP deficit was 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), ath-erosclerotic cardiovascular disease (aHR:1.33 95%CI:1.24-1.43) and coronary heart disease (aHR:1.68 95%CI:1.52-1.86). Early- and later-life height-GaP associations replicated in DMHDS and MESA. Interpretation: This study introduces a simple index of early-life growth adversity deployable in adulthood to investigate the developmental origins of longevity and improve health equity across the life course.

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Research summary

The paper claims that early-life growth adversity, as quantified by the height-GaP index, is associated with increased mortality risk in adulthood. This research is relevant as it explores the developmental origins of health disparities and longevity, potentially addressing root causes of aging-related health issues.

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