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Background <p>Early-life growth adversity is important to later-life health, but precision assessment 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.</p> Methods <p>Data were first analyzed from the Avon Longitudinal Study of Parents and Children (ALSPAC; <i>n</i> = 4582; 56/43% female/male) and UKBiobank (<i>n</i> = 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; <i>n</i> = 855; 49/51% female/male) and the Multi-Ethnic Study of Atherosclerosis (MESA; <i>n</i> = 6352; 52/48% female/male).</p> Results <p>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 (<i>p</i> &lt; 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Raphael Goldman-Pham,
  • Matthew P. Alter,
  • Rebecca Bao,
  • Sophie É. Collins,
  • Catherine L. Debban,
  • James P. Allinson,
  • Antony Ambler,
  • Alain G. Bertoni,
  • Avshalom Caspi,
  • Stephanie Lovinsky-Desir,
  • Magnus P. Ekstrom,
  • James C. Engert,
  • David R. Jacobs Jr,
  • Daniel Malinsky,
  • Ani Manichaikul,
  • Erin D. Michos,
  • Terrie E. Moffitt,
  • Elizabeth C. Oelsner,
  • Sandhya Ramrakha,
  • Stephen S. Rich,
  • Coralynn Sack,
  • Sanja Stanojevic,
  • Padmaja Subbarao,
  • Karen Sugden,
  • Reremoana Theodore,
  • Karol E. Watson,
  • Benjamin Williams,
  • Bin Yang,
  • Josée Dupuis,
  • Seif O. Shaheen,
  • R. Graham Barr,
  • Robert J. Hancox,
  • Benjamin M. Smith

摘要

Background

Early-life growth adversity is important to later-life health, but precision assessment 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; 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.