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The Early Life Course of Body Weight and Gene Expression Signatures for Disease

Cecilia Potente, Kathleen Mullan Harris, Justin Chumbley

    American Journal of Epidemiology
    |March 6, 2021
    PubMed

    Insights

    Body weight patterns across life influence disease gene expression. Birth weight is key for cardiovascular disease and type 2 diabetes, while adult obesity impacts these and inflammation.

    Area of Science:

    • Genomics
    • Epidemiology
    • Life-course studies

    Background:

    • Body-weight patterns throughout life are linked to chronic diseases.
    • Gene expression signatures offer insights into disease mechanisms.

    Purpose of the Study:

    • To investigate the association between body-weight trajectories and gene expression signatures for cardiovascular disease (CVD), type 2 diabetes (T2D), and inflammation.
    • To compare critical/sensitive period models versus accumulation models for these associations.

    Main Methods:

    • Utilized data from the National Longitudinal Study of Adolescent to Adult Health (Wave V, n=1,132).
    • Collected peripheral blood mRNA abundance data.
    • Employed Bayesian modeling to analyze body size at five life stages (birth, adolescence, early adulthood, young adulthood, adulthood) against gene expression disease signatures.

    Main Results:

    • Findings support a sensitive-period model for CVD and T2D gene expression signatures.
    • Birth weight significantly influences CVD (33.1%) and T2D (22.1%) signatures.
    • Adult obesity (ages 33-39) is crucial for CVD (24.3%) and T2D (35.1%) signatures.
    • Body size across all life stages is associated with inflammation, aligning with an accumulation model.

    Conclusions:

    • Early life body size (birth weight) and later life obesity are critical determinants of CVD and T2D gene expression.
    • Inflammation gene expression is influenced by cumulative body size throughout life.
    • These findings highlight distinct temporal patterns in how body weight impacts disease-related gene expression.

    Keywords:
    birth weightcardiovascular diseasegene expressioninflammationlife courseobesitytype 2 diabetes

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