# Distinct genetic profiles influence body mass index between infancy and adolescence

**Authors:** Geng Wang, Samuel McEwan, Jian Zeng, Mekonnen Haile-Mariam, Loic Yengo, Michael E. Goddard, Kathryn E. Kemper, Nicole M. Warrington

PMC · DOI: 10.1038/s41467-026-69310-6 · Nature Communications · 2026-02-19

## TL;DR

This study finds that genetic influences on body mass index (BMI) change as children grow from infancy to adolescence.

## Contribution

The study introduces a random regression model to reveal age-specific genetic effects on BMI trajectories.

## Key findings

- SNP-based heritability of BMI at age 9.5 is 28.4%, and the rate of BMI change has a heritability of 23.8%.
- Genetic correlations between early childhood and adolescence are low (0.108).
- Two genetic axes explain most of the variation in BMI trajectories, with opposing effects in early and later ages.

## Abstract

Body mass index (BMI) changes throughout life with age-varying genetic contributions. We use a random regression model to investigate the genetic contribution to BMI trajectories from ages one to 18 years in 6,291 ALSPAC participants with 65,930 repeated BMI measurements. Here we show the estimated SNP-based heritability of BMI at 9.5 years is 28.4% (SE = 4.8%), and 23.8% (SE = 4.2%) for rate of change in BMI from one to 18 years. The genetic correlations between early childhood and adolescence are low (genetic correlation between two and 17 years is 0.108 [SE = 0.146]). We find that the first principal component of the trajectory, explaining 89% of genetic variation, captures effects which increase in magnitude from early childhood to adolescence and then plateau. A second axis explaining 9% of the genetic variance has opposite effects on BMI between early and later ages. Our findings demonstrate the value of RRMs to reveal age-specific genetic influences on BMI across development.

Using a random regression model, the study shows there are varying genetic profiles that act on BMI from infancy to adolescence. Change in BMI across childhood is genetically correlated with several adult cardiometabolic traits.

## Full-text entities

- **Genes:** LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 5122] {aka BMIQ12, NEC1, PC1, PC1/3, PC3, SPC3}, FTO (FTO alpha-ketoglutarate dependent dioxygenase) [NCBI Gene 79068] {aka ALKBH9, BMIQ14, GDFD, IFEX9}, APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}, ADCY3 (adenylate cyclase 3) [NCBI Gene 109] {aka AC-III, AC3, BMIQ19}, CBX4 (chromobox 4) [NCBI Gene 8535] {aka NBP16, PC2}, LEPR (leptin receptor) [NCBI Gene 3953] {aka CD295, LEP-R, LEPRD, OB-R, OBR, huB219}, OLFM4 (olfactomedin 4) [NCBI Gene 10562] {aka GC1, GW112, OLM4, OlfD, UNQ362, bA209J19.1}
- **Diseases:** type 2 diabetes (MESH:D003924), underweight (MESH:D013851), adiposity (MESH:D018205), RRM (MESH:C537770), hypertension (MESH:D006973), cardio-metabolic diseases (MESH:D008659), BMI (MESH:C536030), weight gain (MESH:D015430), Obesity (MESH:D009765), disease (MESH:D004194)
- **Chemicals:** glucose (MESH:D005947), cholesterol (MESH:D002784), triglycerides (MESH:D014280)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs10203482, rs55872725, rs4477562, rs9972653

## Full text

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## Figures

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## References

4 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920650/full.md

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Source: https://tomesphere.com/paper/PMC12920650