From modeling to measurement: Developmental trends in genetic influence on adiposity in childhood

Authors

  • C.H. Llewellyn,

    Corresponding author
    1. Health Behavior Research Center, Department of Epidemiology & Public Health, University College London, UK
    2. MRC Social, Genetic and Developmental Psychiatry Center, Institute of Psychiatry, King's College London, UK
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    • C.H. Llewellyn and M. Trzaskowski contributed equally to the manuscript.

  • M. Trzaskowski,

    1. MRC Social, Genetic and Developmental Psychiatry Center, Institute of Psychiatry, King's College London, UK
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    • C.H. Llewellyn and M. Trzaskowski contributed equally to the manuscript.

  • R. Plomin,

    1. MRC Social, Genetic and Developmental Psychiatry Center, Institute of Psychiatry, King's College London, UK
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  • J. Wardle

    1. Health Behavior Research Center, Department of Epidemiology & Public Health, University College London, UK
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  • Funding agencies: The Twins Early Development Study (TEDS) is supported by a program grant to Robert Plomin from the UK Medical Research Council [G0901245; and previously G0500079], with additional support from the US National Institutes of Health [HD044454; HD059215]. The anthropometric data were collected as part of a grant to Jane Wardle from the UK Biological and Biotechnology Research Council [D19086] with additional support from program grant funding from Cancer Research UK. Genome-wide genotyping was made possible by grants from the Wellcome Trust Case Control Consortium 2 project [085475/Z/08/Z].

  • Disclosure: All authors declare no conflicts of interest.

  • Author contributions: CL, MT, and JW designed the study; CL and MT analyzed the data and drafted the manuscript. RP and JW contributed to data interpretation. All authors were involved in writing the article and had final approval of the submitted and published versions.

Abstract

Objective

Evidence of increasing heritability of BMI over childhood can seem paradoxical given longer exposure to environmental influences. Genomic data were used to provide direct evidence of developmental increases in genetic influence.

Methods

BMI standard deviation scores (BMI-SDS) at ages 4 and 10 were calculated for 2,556 twin pairs in the Twins Early Development Study. Twin analyses estimated heritability of BMI-SDS at each age and the longitudinal genetic correlation. One randomly selected twin per pair was genotyped. Genome-wide complex trait analysis (GCTA) determined DNA-based heritability at each age and the longitudinal genomic correlation. Associations with a polygenic obesity risk score (PRS) using 28 obesity-related single nucleotide polymorphisms (SNPs) were assessed at each age, with bootstrapping to test the significance of the increase in variance explained.

Results

Twin-estimated heritability increased from age 4 (0.43; 95% CI: 0.35-0.53) to 10 (0.82; 0.74-0.88). GCTA-estimated heritability went from non-significant at 4 (0.20; −0.21 to 0.61) to significant at 10 (0.29; 0.01-0.57). Longitudinal genetic correlations derived from twins (0.58) and GCTA (0.66) were similar. The same PRS explained more variance at 10 than 4 years (R2 Δ:0.024; 0.002-0.078).

Conclusions

GCTA and PRS findings confirm twin-based results suggesting increasing genetic influence on adiposity during childhood despite substantial genetic stability.

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