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Genetics and Epigenetics

The heritability of BMI varies across the range of BMI—a heritability curve analysis in a twin cohort

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Abstract

Background

The heritability of traits such as body mass index (BMI), a measure of obesity, is generally estimated using family and twin studies, and increasingly by molecular genetic approaches. These studies generally assume that genetic effects are uniform across all trait values, yet there is emerging evidence that this may not always be the case.

Method/Subjects

This paper analyzes twin data using a recently developed measure of heritability called the heritability curve. Under the assumption that trait values in twin pairs are governed by a flexible Gaussian mixture distribution, heritability curves may vary across trait values. The data consist of repeated measures of BMI on 1506 monozygotic (MZ) and 2843 like-sexed dizygotic (DZ) adult twin pairs, gathered from multiple surveys in older Finnish Twin Cohorts.

Results

The heritability curve and BMI value-specific MZ and DZ pairwise correlations were estimated, and these varied across the range of BMI. MZ correlations were highest at BMI values from 21 to 24, with a stronger decrease for women than for men at higher values. Models with additive and dominance effects fit best at low and high BMI values, while models with additive genetic and common environmental effects fit best in the normal range of BMI.

Conclusions

We demonstrate that twin and molecular genetic studies need to consider how genetic effects vary across trait values. Such variation may reconcile findings of traits with high heritability and major differences in mean values between countries or over time.

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Fig. 1: Regression analysis used to estimate \({{{\boldsymbol{BMI}}}}_{35}\) (BMI at age 35) for each of 8598 individuals in the study.
Fig. 2: \({{{\boldsymbol{BMI}}}}_{35}\) for pairs of female dizygotic twins, obtained by regression analysis.
Fig. 3: Correlation curves for male and female data for monozygotic (top) and dizygotic (bottom) twins, with pointwise 95% confidence bands (shaded regions).
Fig. 4: Decomposition of total variance into genetic and environmental effects by BMI, sex, and genetic model (ACE in red; ADE in blue).

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Data availability

The FTC data is not publicly available due to the restrictions of informed consent. However, the FTC data is available through the Institute for Molecular Medicine Finland (FIMM) Data Access Committee (DAC) (fimm-dac@helsinki.fi) for authorized researchers who have IRB/ethics approval and an institutionally approved study plan. To ensure the protection of privacy and compliance with national data protection legislation, a data use/transfer agreement is needed, the content and specific clauses of which will depend on the nature of the requested data.

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Acknowledgements

Parts of this work have been done in the context of CEDAS (Center for Data Science, University of Bergen, Norway).

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Authors and Affiliations

  1. Department of Mathematics, University of Bergen, Bergen, Norway

    Francesca Azzolini & Hans J. Skaug

  2. Department of Business and Management Science, NHH Norwegian School of Economics, Bergen, Norway

    Geir D. Berentsen

  3. Department of Public Health, University of Southern Denmark, Odense, Denmark

    Jacob V. B. Hjelmborg

  4. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    Jaakko A. Kaprio

Authors
  1. Francesca Azzolini
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Contributions

FA, GDB, HJS and JBH contributed to the conception and design of the work. JBH and JAK provided the data material. FA carried out all statistical analyses. FA drafted the manuscript, except for sections Introduction and Discussion which were drafted by JAK. All authors participated in finalizing the manuscript and gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.

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Correspondence to Francesca Azzolini.

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Azzolini, F., Berentsen, G.D., Skaug, H.J. et al. The heritability of BMI varies across the range of BMI—a heritability curve analysis in a twin cohort. Int J Obes 46, 1786–1791 (2022). https://doi.org/10.1038/s41366-022-01172-6

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