Body mass index (BMI) changes throughout life with age-varying genetic contributions. We aimed to investigate the genetic contribution to BMI across early life using repeated measures from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Random regression modelling was used to estimate the genetic covariance matrix (Kg) of BMI trajectories from ages one to 18 years with 65,930 repeated BMI measurements from 6,291 genotyped ALSPAC participants. The Kg matrix was used to estimate SNP-based heritability at yearly intervals from 1-18 years and genetic correlations across early life. We also performed an eigenvalue decomposition of Kg to identify age-varying genetic patterns of BMI. Finally, we investigated the impact of a polygenic score derived from adult BMI on the estimated genetic components across early life. The was relatively constant across early life, between 23-30%. The genetic contribution to BMI in early childhood is different to that in later childhood, indicated by the diminishing strength of genetic correlation across different ages. The eigenvalue decomposition revealed that the primary axis of variation (explaining 89% of the genetic variance in Kg) increases with age from zero and reaches a plateau in adolescence, while the second eigenfunction (explaining around 9% of Kg) represents factors with opposing effects on BMI between early and later ages. Adjusting for the adult BMI polygenic score attenuated the from late childhood; for example, is 29.8% (SE=6.5%) at 18 years of age and attenuates to 14.5% (SE=6.3%) after adjusting for the adult BMI polygenic score. Although common genetic variation explains around 23-30% of BMI variability across early life, our findings indicate that there is a different genetic profile operating during infancy compared to later childhood and adolescence.

The authors have declared no competing interest.

G.W. and N.M.W. are funded by a National Health and Medical Research Council (Australia) Investigator grant (APP2008723). K.E.K. was supported by the Australian Research Council (grant FL180100072). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. GWAS data in ALSPAC was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. A comprehensive list of funding provided to ALSPC from grants is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by Wellcome Trust and MRC (core), 076467/Z/05/Z.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Avon Longitudinal Study of Parents and Children Ethics and Law Committee and the Local Research Ethics Committees gave ethical approval for this work. The Institutional Human Research Ethics Committee of the University of Queensland gave ethical approval for this work.

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