Characterizing the Causal Pathway From Childhood Adiposity to Right Heart Physiology and Pulmonary Circulation Using Lifecourse Mendelian Randomization

Genevieve M Leyden, Helena Urquijo, Alun D Hughes, George Davey Smith, Tom G Richardson*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review


Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging.

Methods and Results
In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end‐diastolic volume: β=0.24 [95% CI, 0.15–0.33]; P=3×10−7) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat‐free mass and childhood height, respectively.

Our findings suggest that, although childhood body size has a long‐term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse.
Original languageEnglish
Article numbere030453
Pages (from-to)e030453
JournalJournal of the American Heart Association
Issue number6
Publication statusPublished - 8 Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Structured keywords

  • Bristol Population Health Science Institute


  • lifecourse epidemiology
  • Mendelian randomization
  • childhood adiposity


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  • Integrative Epidemiology Unit

    Gaunt, L. F.


    Project: Research

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