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Epidemiology and Population Health

Preschool age-specific obesity and later-life kidney health: a Mendelian randomization and colocalization study

International Journal of Obesity volume 49, pages 649–657 (2025)Cite this article

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Abstract

Objectives

While the association between obesity and kidney diseases has been found in previous studies, the relationship between preschool-age obesity and later-life kidney health remains unclear, posing challenges for effective interventions in this critical life period.

Methods

Utilizing the hitherto largest genome-wide association studies, we conducted two-sample mendelian randomization (MR) to estimate the association of preschool age-specific obesity on kidney health and diseases, including blood urea nitrogen (BUN), eGFRcrea, eGFRcys, chronic kidney disease (CKD), IgA nephropathy, and diabetic nephropathy. Then, we applied multivariable Mendelian randomization (MVMR) and stepwise MR to elucidate the role of adult obesity and 12 other potential factors in the pathway between preschool age-specific obesity and kidney health. Finally, we employed colocalization analysis to understand the mechanism of preschool age-specific obesity and kidney damage further by detecting shared causal variants.

Results

Our two-sample MR results indicated that preschool obesity could be associated with kidney health and disease. In addition, we observed a switch in the direction of associations between age-specific body mass index (BMI) and CKD, manifesting as negative associations before 3 years old and positive associations after 3 years old. Furthermore, MVMR and stepwise MR results suggested potential pathways linking preschool obesity to kidney health, involving factors such as adult BMI, circulating high-density lipoprotein cholesterol levels, and circulating C-reactive protein levels. Finally, we detected that preschool-age BMI and kidney function could share causal variants such as rs76111507, rs62107261, rs77165542 in the region of chromosome 2, and rs571312 in the region of chromosome 18.

Conclusion

Our study supports the association between preschool obesity and kidney health, emphasizing the role of adult BMI in this relationship. These findings underscore the importance of interventions starting in early childhood and continuing through adulthood to reduce the long-term risk of obesity-related kidney damage.

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Fig. 1: The design and methods used in this Mendelian randomization study.
Fig. 2: The IVW results of preschool age-specific obesity and kidney health and disease.
Fig. 3: The MVMR results of preschool age-specific obesity to eGFRcys.
Fig. 4: The putative pathway linking preschool obesity, adult obesity, correspondence candidate mediator, and kidney health in stepwise MR.
Fig. 5: The colocalization results of SNPs with PPH4 ≥ 0.75 and their sensitivity analysis results.

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Data availability

Summary statistics of birth weight and overall childhood BMI were downloaded from http://egg-consortium.org. Summary statistics of preschool age-specific BMI were downloaded from https://www.fhi.no/en/studies/moba/for-forskere-artikler/gwas-data-from-moba/. Summary statistics for CKDGen Consortium were obtained from https://ckdgen.imbi.uni-freiburg.de. The summary statistics of IgA nephropathy were obtained from the Scania Diabetes Registry (SDR), Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) study, Steno Diabetes Centre, and Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) A and B studies, which can be obtained from https://humandbs.biosciencedbc.jp/en/hum0197-v3-220. The summary statistics of diabetic nephropathy can be found on the website GWAS Catalog (http://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/GCST005001-GCST006000/GCST005880/).

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Acknowledgements

We express our gratitude to the patients and investigators who have contributed to the EGG Consortium, the CKDGen Consortium, MoBa Cohort, the Scania Diabetes Registry (SDR), Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) study, Steno Diabetes Centre, and Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) A and B studies.

Funding

This study was supported by the National Natural Science Foundation of China (U20A20411, Zhenmi Liu), the Fundamental Research Funds for the Central Universities (2022SCU12021, Chenghan Xiao), and the Natural Science Foundation of Sichuan Province (2023NSFSC0652, Ling Zhang). The funders played no role in the design of the study, collection and analysis of data, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China

    Xin Jin, Yujue Wang, Sixuan Zeng, Qiaoyue Ge, Lu Zhang, Xinxi Li, Xiaoli Luo, Menghan Yang, Weidong Zhang, Chuan Yu, Chenghan Xiao & Zhenmi Liu

  2. Faculty of Medicine, Imperial College London, London, UK

    Jiarui Cai

  3. Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China

    Kerui Wang

  4. Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China

    Ling Zhang, Chenghan Xiao & Zhenmi Liu

  5. Med-X center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu, China

    Ling Zhang

  6. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

    Yu Tong

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  1. Xin Jin
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Contributions

Xin Jin: conceptualization, formal analysis, visualization, writing—original draft, writing—review and editing. Yujue Wang, Sixuan Zeng, Jiarui Cai, Kerui Wang, Xinxi Li, Yu Tong, Xiaoli Luo, Menghan Yang, and Weidong Zhang: writing—review and editing. Qiaoyue Ge and Lu Zhang verified data. Chuan Yu: conceptualization, writing—review and editing. Ling Zhang: funding acquisition, writing—review and editing. Chenghan Xiao and Zhenmi Liu: conceptualization, funding acquisition, writing—review and editing. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Chuan Yu, Chenghan Xiao or Zhenmi Liu.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study adheres to STROBE-MR Guidelines and each included GWAS has institutional review board approval and participant consent. The UK Biobank has ethics approval from the North West Multi-Centre Research Ethics Committee. Age-specific BMI GWAS received ethical approval from the Avon Longitudinal Study of Parents and Children (ALSPAC) Ethics and Law Committee and Local Research Ethics Committees, with consent under the Human Tissue Act (2004). MoBa’s study protocol was approved by the Norwegian Institute of Public Health’s administrative board, with data collection authorized by the Norwegian Data Protection Agency and The Regional Committee for Medical Research Ethics (no. 2012/67). The Amsterdam Born Children and their Development- Genetic Enrichment (ABCD) study protocol received approval from the Dutch Central Committee on Research Involving Human Subjects, the medical ethics review committees of the hospitals involved, and the Amsterdam Municipality’s Registration Committee.

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Jin, X., Wang, Y., Zeng, S. et al. Preschool age-specific obesity and later-life kidney health: a Mendelian randomization and colocalization study. Int J Obes 49, 649–657 (2025). https://doi.org/10.1038/s41366-024-01686-1

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