The impact of age-specific childhood body-mass index on adult cardiometabolic traits: a Mendelian randomization study

Jun Yang; Yalan Kuang; Xiaoyan Yang; Chunyang Li; Mei Qi; Ping Fu; Xiaoxi Zeng

doi:10.3389/fendo.2023.1159547

The impact of age-specific childhood body-mass index on adult cardiometabolic traits: a Mendelian randomization study

Front Endocrinol (Lausanne). 2024 Jan 15:14:1159547. doi: 10.3389/fendo.2023.1159547. eCollection 2023.

Authors

Jun Yang¹, Yalan Kuang², Xiaoyan Yang², Chunyang Li², Mei Qi³, Ping Fu⁴, Xiaoxi Zeng^{2

4}

Affiliations

¹ Department of Mathematics, Med-X Center for Informatics, Sichuan University, Chengdu, China.
² West China Biomedical Big Data Center, West China Hospital, Chengdu, China.
³ Division of Nephrology, The Second People's Hospital of Tibet Autonomous Region, Lhasa, China.
⁴ Division of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Objective: To evaluate the causal relationship between childhood body-mass index (BMI) at different ages and adult cardiometabolic traits.

Methods: We retrieved genetic instrument variables (IVs) for exposures (standardized BMI at newborn, infant, toddler and late childhood), cardiometabolic traits and potential confounders or mediators (adult BMI, SHBG, testosterone and age at menarche) from the corresponding genome-wide association analysis. We performed univariate and multivariable Mendelian randomization (MR) to dissect associations between age-specific childhood BMI and adult cardiometabolic outcomes. Odds ratio was used to present the direction of the causal association.

Results: In univariate MR, higher newborn BMI was causally associated with reduced risk for type 2 diabetes in women. Late childhood BMI was associated with increased risk for female diabetes and coronary artery disease (CAD), myocardial infarction (MI), and chronic kidney disease (CKD) in general population. Among these associations, only association between late childhood BMI with MI remained significant after adjusting for adult male BMI and sex hormones, (OR = 1.120, 95% CI 1.023-1.226, p = 0.014). Besides, in multivariable MR, we found evidence for causal association between newborn BMI with reduced risk for CAD (OR = 0.862, 95% CI 0.751-0.989, p = 0.034) and MI (OR = 0.864, 95% CI 0.752-0.991, p = 0.037) in men. No obvious impact of infant or toddler BMI was identified on the above-mentioned diseases. For continuous cardiometabolic traits, in all age epochs except infant, higher BMI was associated with increased level of fasting glucose in women.

Conclusion: BMI at birth and late childhood exerts different impact on adult cardiometabolic diseases, while BMI at infant and toddler ages is not causally associated with these outcomes. The effect of childhood BMI may be influenced by sex disparities.

Keywords: Mendelian randomization; body mass index; cardiometabolic traits; childhood; genome-wide association study; sex disparity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age Factors
Body Mass Index
Cardiometabolic Risk Factors
Child
Coronary Artery Disease* / genetics
Diabetes Mellitus, Type 2* / epidemiology
Diabetes Mellitus, Type 2* / genetics
Female
Genome-Wide Association Study
Humans
Infant, Newborn
Male
Mendelian Randomization Analysis

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Among the authors, XZ and MQ were supported by Science and Technology Department of Sichuan Province (2021YF0035) and the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC18010).