Mediation and moderation of genetic risk of obesity through eating behaviours in two UK cohorts

Shahina Begum*, Eleanor Hinton, Zoi Toumpakari, Timothy M Frayling, Laura D Howe, Laura Johnson, Natalia Lawrence

*Corresponding author for this work

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

1 Citation (Scopus)


The mechanisms underlying genetic predisposition to higher body mass index (BMI) remain unclear.

We hypothesized that the relationship between BMI-genetic risk score (BMI-GRS) and BMI was mediated via disinhibition, emotional eating and hunger, and moderated by flexible (but not rigid) restraint within two UK cohorts: the Genetics of Appetite Study (GATE) (n = 2101, 2010–16) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 1679, 2014–18). Eating behaviour was measured by the Adult Eating Behaviour Questionnaire and Three-Factor Eating Questionaire-51.

The association between BMI-GRS and BMI were partially mediated by habitual, emotional and situational disinhibition in the GATE/ALSPAC meta-mediation [standardized betaindirect 0.04, 95% confidence interval (CI) 0.02–0.06; 0.03, 0.01–0.04; 0.03, 0.01–0.04, respectively] external hunger and internal hunger in the GATE study (0.02, 0.01–0.03; 0.01, 0.001–0.02, respectively). There was evidence of mediation by emotional over/undereating and hunger in the ALSPAC study (0.02, 0.01–0.03; 0.01, 0.001–0.02; 0.01, 0.002–0.01, respectively). Rigid or flexible restraint did not moderate the direct association between BMI-GRS and BMI, but high flexible restraint moderated the effect of disinhibition subscales on BMI (reduction of the indirect mediation by -5% to -11% in GATE/ALSPAC) and external hunger (-5%) in GATE. High rigid restraint reduced the mediation via disinhibition subscales in GATE/ALSPAC (-4% to -11%) and external hunger (-3%) in GATE.

Genetic predisposition to a higher BMI was partly explained by disinhibition and hunger in two large cohorts. Flexible/rigid restraint may play an important role in moderating the impact of predisposition to higher BMI.
Original languageEnglish
Article numberdyad092
Pages (from-to)1926-1938
Number of pages13
JournalInternational Journal of Epidemiology
Issue number6
Early online date6 Jul 2023
Publication statusPublished - 1 Dec 2023

Bibliographical note

Funding Information:
This work was supported in part by grant MR/N0137941/1 for the Great Western 4 Biomed Medical Research Council (MRC) Doctoral Training Partnership, awarded to the Universities of Bath, Bristol, Cardiff and Exeter from the MRC/UK Research and Innovation. The GATE study is supported by the National Institute for Health and Care Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol and European Research Council (T.M.F., grant ref: 323195: GLUCOSEGENES-FP7-IDEAS-ERC). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors will serve as guarantors for the contents of this paper. Research for ALSPAC was specifically funded by the MRC and Kellog Europe (PI L.H. and L.J., grant ref: SPOL.RM8475 and G1002375). L.D.H. is funded by a UK Medical Research Council fellowship [MR/M020894/1]. Acknowledgements

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


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