Endocrine Abstracts

JOINT2746

Objective: Observational studies have reported that childhood body mass index (BMI) affects height growth patterns without significantly effecting adult stature. The causal relationship remain unclear. Mendelian randomization (MR)—a genetic instrumental variable approach leveraging Mendel’s second law to minimize confounding—was employed to assess causality between childhood BMI and height growth patterns, including pre-pubertal growth (age≤10 years), total pubertal height growth, late pubertal height growth, and adult stature, (standing and sitting height).

Methods: Adhering to the STROBE-MR guidelines. Whole genome-wide association study (GWAS) data were extracted from the MRC-IEU GWAS database (https://gwas.mrcieu.ac.uk). Causal estimates were derived using inverse variance weighting (IVW) as the primary method, supplemented by MR–Egger regression, weighted median, weighted mode, and simple mode analyses. Sensitivity analyses included Cochran’s Q test for heterogeneity, MR–Egger’s intercept and the MR-PRESSO test for pleiotropy assessment, and leave-one-out SNPs exclusion to evaluate robustness.

Results: MR analyses revealed childhood BMI exhibited a positive causal effect on pre-pubertal height growth (β=0.11, 95%CI [0.08, 0.13], P=1.13×10⁻¹³). But inversely negative correlated with total pubertal height growth (males: β=-0.40, 95%CI: [-0.61, -0.18], P=2.64×10^-4; females: β=-0.61, 95%CI: [-0.85, -0.36]; P=9.49×10^-7), late pubertal height growth (males:β=-0.52, 95%CI: [-0.75, -0.28], P=2.46×10^-5; females: β=-0.45; 95%CI: [-0.68, -0.21], P=2.02×10^-4). No significant link between childhood BMI and adult standing or sitting height. Sensitivity analysis revealed absence of horizontal pleiotropy (MR-Egger intercept P>0.05) and outlier SNPs (MR-PRESSO P>0.05), with leave-one-out’ tests demonstrating results stablity.

Conclusion: This study demonstrates dual-phase effects: positively influencing early childhood height acceleration but suppressing pubertal growth trajectories. These transient effects resolve by adulthood, with no measurable impact on final stature. Findings underscore BMI’s role as a modulator of developmental tempo rather than a determinant of adult height.

Keywords Mendelian randomization, Childhood BMI, Height growth pattern, Adult stature