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Pediatrics

Elucidating pathways to pediatric obesity: a study evaluating obesity polygenic risk scores related to appetitive traits in children

International Journal of Obesity (2023)Cite this article

Subjects

Abstract

Background/Objectives

Obesity polygenic risk scores (PRS) explain substantial variation in body mass index (BMI), yet associations between PRSs and appetitive traits in children remain unclear. To better understand pathways leading to pediatric obesity, this study aimed to assess the association of obesity PRSs and appetitive traits.

Subjects/Methods

This study included 248 unrelated children aged 9–12 years. DNA from the children was genotyped (236 met quality control thresholds) and four weighted polygenic risk scores from previous studies were computed and standardized: a 97 SNP PRS, 266 SNP pediatric-specific PRS, 466 SNP adult-specific PRS, and ~2 million SNP PRS. Appetitive traits were assessed using a parent-completed Child Eating Behavior Questionnaire, which evaluated food approach/avoidance traits and a composite obesogenic appetite score. BMI was directly measured and standardized by age and sex. Three associations were evaluated with linear regression: (1) appetitive traits and BMI, (2) PRSs and BMI, and (3) PRSs and appetitive traits, the primary association of interest.

Results

Expected positive associations were observed between obesogenic appetitive traits and BMI and all four PRSs and BMI. Examining the association between PRSs and appetitive traits, all PRSs except for the 466 SNP adult PRS were significantly associated with the obesogenic appetite score. Each standard deviation increase in the 266 SNP pediatric PRS was associated with an adjusted 2.1% increase in obesogenic appetite score (95% CI: 0.6%, 3.7%, p = 0.006). Significant partial mediation of the PRS-BMI association by obesogenic appetite score was found for these PRSs; for example, 21.3% of the association between the 266 SNP pediatric PRS and BMI was explained by the obesogenic appetite score.

Conclusions

Genetic obesity risk significantly predicted appetitive traits, which partially mediated the association between genetic obesity risk and BMI in children. These findings build a clearer picture of pathways leading to pediatric obesity.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This research was supported by National Institutes of Health grants 1R01HD092604 and 1R21HD076097 (DG-D). We thank the Dartmouth Cancer Center Genomics Shared Resource (especially Fred Kolling, PhD and Owen Wilkins, PhD) for assistance processing global screening arrays. The Dartmouth Cancer Center Genomics Shared Resource was supported by 5P30CA023108 and P20GM130454.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Timothy J. Renier, Dabin Yeum, Reina K. Lansigan, Grace A. Ballarino, Delaina D. Carlson & Diane Gilbert-Diamond

  2. Department of Biomedical Data Sciences, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Jennifer A. Emond

  3. Department of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Jennifer A. Emond & Diane Gilbert-Diamond

  4. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Ruth J. F. Loos

  5. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

    Ruth J. F. Loos

  6. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Ruth J. F. Loos

  7. Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Diane Gilbert-Diamond

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Contributions

DG-D, JAE, and RKL contributed to the study concept and design. TJR, DG-D, JAE, and DY contributed to statistical analysis. TJR drafted the manuscript. All authors contributed to data acquisition, analysis, or interpretation, and critically reviewed and approved this manuscript. DG-D obtained funding. RKL, GAB, and DDC provided administrative, technical, or material support.

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Correspondence to Timothy J. Renier.

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Renier, T.J., Yeum, D., Emond, J.A. et al. Elucidating pathways to pediatric obesity: a study evaluating obesity polygenic risk scores related to appetitive traits in children. Int J Obes (2023). https://doi.org/10.1038/s41366-023-01385-3

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