Life course effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study

Scott Waterfield*, Tom G Richardson, George Davey Smith, Linda M O’Keeffe, Joshua A Bell

*Corresponding author for this work

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

9 Citations (Scopus)

Abstract

Background/objectives

Different genetic variants are associated with larger body size in childhood vs adulthood. Whether and when these variants predominantly influence adiposity are unknown. We examined how genetic variants influence total body fat and total lean mass trajectories.
Methods

Data were from the Avon Longitudinal Study of Parents and Children birth cohort (N = 6926). Sex-specific genetic risk scores (GRS) for childhood and adulthood body size were generated, and dual-energy X-ray absorptiometry scans measured body fat and lean mass six times between the ages of 9 and 25 years. Multilevel linear spline models examined associations of GRS with fat and lean mass trajectories.
Results

In males, the sex-specific childhood and adulthood GRS were associated with similar differences in fat mass from 9 to 18 years; 8.3% [95% confidence interval (CI) 5.1, 11.6] and 7.5% (95% CI 4.3, 10.8) higher fat mass at 18 years per standard deviation (SD) higher childhood and adulthood GRS, respectively. In males, the sex-combined childhood GRS had stronger effects at ages 9 to 15 than the sex-combined adulthood GRS. In females, associations for the sex-specific childhood GRS were almost 2-fold stronger than the adulthood GRS from 9 to 18 years: 10.5% (95% CI 8.5, 12.4) higher fat mass at 9 years per SD higher childhood GRS compared with 5.1% (95% CI 3.2, 6.9) per-SD higher adulthood GRS. In females, the sex-combined GRS had similar effects, with slightly larger effect estimates. Lean mass effect sizes were much smaller.
Conclusions

Genetic variants for body size are more strongly associated with adiposity than with lean mass. Sex-combined childhood variants are more strongly associated with increased adiposity until early adulthood. This may inform future studies that use genetics to investigate the causes and impact of adiposity at different life stages.
Original languageEnglish
Article numberdyad029
Pages (from-to)1377–1387
Number of pages11
JournalInternational Journal of Epidemiology
Volume52
Issue number5
Early online date23 Mar 2023
DOIs
Publication statusPublished - 1 Oct 2023

Bibliographical note

Funding Information:
S.W. is supported by Cancer Research UK (grant number C18281/A30905). T.G.R., G.D.S. and J.A.B. work in a unit funded by the UK MRC (MC_UU_00011/1) and the University of Bristol. L.M.O.K. is supported by a Health Research Board (HRB) of Ireland Emerging Investigator Award (EIA-FA-2019–007 SCaRLeT). The UK Medical Research Council and Wellcome (grant ref.: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website [ http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ] and GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This publication is the work of the authors and S.W. is the guarantor for its contents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgements

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the International Epidemiological Association.

Research Groups and Themes

  • ICEP
  • Bristol Population Health Science Institute

Fingerprint

Dive into the research topics of 'Life course effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study'. Together they form a unique fingerprint.

Cite this