Slavskii, Sergei A.; Kuznetsov, Ivan A.; Shashkova, Tatiana I.; Bazykin, Georgii A.; Axenovich, Tatiana I.; Kondrashov, FyodorIST Austria ; Aulchenko, Yurii S.
Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait.
European Journal of Human Genetics
We are grateful to Marianna Bevova and Pavel Borodin for fruitful discussion and help with conceptualising our findings and to Lennart C. Karssen for help with handling the UK Biobank data. Funding This research has been conducted using the UK Biobank Resource (project # 41601, “Non-additive effects in control of complex human traits”). The work of SAS, IAK, and TIS were supported by Russian Ministry of Science and Education under the 5–100 Excellence Programme. The work of YSA and TIA was supported by the Ministry of Education and Science of the RF via the Institute of Cytology and Genetics SB RAS (project number 0324-2019-0040-C-01/AAAA-A17-117092070032-4). FAK is supported by the ERC Consolidator Grant (ChrFL: 771209).
Slavskii SA, Kuznetsov IA, Shashkova TI, et al. The limits of normal approximation for adult height. European Journal of Human Genetics. 2021;29(7):1082-1091. doi:10.1038/s41431-021-00836-7
Slavskii, S. A., Kuznetsov, I. A., Shashkova, T. I., Bazykin, G. A., Axenovich, T. I., Kondrashov, F., & Aulchenko, Y. S. (2021). The limits of normal approximation for adult height. European Journal of Human Genetics. Springer Nature. https://doi.org/10.1038/s41431-021-00836-7
Slavskii, Sergei A., Ivan A. Kuznetsov, Tatiana I. Shashkova, Georgii A. Bazykin, Tatiana I. Axenovich, Fyodor Kondrashov, and Yurii S. Aulchenko. “The Limits of Normal Approximation for Adult Height.” European Journal of Human Genetics. Springer Nature, 2021. https://doi.org/10.1038/s41431-021-00836-7.
S. A. Slavskii et al., “The limits of normal approximation for adult height,” European Journal of Human Genetics, vol. 29, no. 7. Springer Nature, pp. 1082–1091, 2021.
Slavskii SA, Kuznetsov IA, Shashkova TI, Bazykin GA, Axenovich TI, Kondrashov F, Aulchenko YS. 2021. The limits of normal approximation for adult height. European Journal of Human Genetics. 29(7), 1082–1091.
Slavskii, Sergei A., et al. “The Limits of Normal Approximation for Adult Height.” European Journal of Human Genetics, vol. 29, no. 7, Springer Nature, 2021, pp. 1082–91, doi:10.1038/s41431-021-00836-7.
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