---
_id: '9910'
abstract:
- lang: eng
  text: 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.
acknowledgement: "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.\r\n\r\nFunding\r\nThis 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)."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Sergei A.
  full_name: Slavskii, Sergei A.
  last_name: Slavskii
- first_name: Ivan A.
  full_name: Kuznetsov, Ivan A.
  last_name: Kuznetsov
- first_name: Tatiana I.
  full_name: Shashkova, Tatiana I.
  last_name: Shashkova
- first_name: Georgii A.
  full_name: Bazykin, Georgii A.
  last_name: Bazykin
- first_name: Tatiana I.
  full_name: Axenovich, Tatiana I.
  last_name: Axenovich
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Yurii S.
  full_name: Aulchenko, Yurii S.
  last_name: Aulchenko
citation:
  ama: Slavskii SA, Kuznetsov IA, Shashkova TI, et al. The limits of normal approximation
    for adult height. <i>European Journal of Human Genetics</i>. 2021;29(7):1082-1091.
    doi:<a href="https://doi.org/10.1038/s41431-021-00836-7">10.1038/s41431-021-00836-7</a>
  apa: Slavskii, S. A., Kuznetsov, I. A., Shashkova, T. I., Bazykin, G. A., Axenovich,
    T. I., Kondrashov, F., &#38; Aulchenko, Y. S. (2021). The limits of normal approximation
    for adult height. <i>European Journal of Human Genetics</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41431-021-00836-7">https://doi.org/10.1038/s41431-021-00836-7</a>
  chicago: 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.” <i>European Journal of Human
    Genetics</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41431-021-00836-7">https://doi.org/10.1038/s41431-021-00836-7</a>.
  ieee: S. A. Slavskii <i>et al.</i>, “The limits of normal approximation for adult
    height,” <i>European Journal of Human Genetics</i>, vol. 29, no. 7. Springer Nature,
    pp. 1082–1091, 2021.
  ista: 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.
  mla: Slavskii, Sergei A., et al. “The Limits of Normal Approximation for Adult Height.”
    <i>European Journal of Human Genetics</i>, vol. 29, no. 7, Springer Nature, 2021,
    pp. 1082–91, doi:<a href="https://doi.org/10.1038/s41431-021-00836-7">10.1038/s41431-021-00836-7</a>.
  short: S.A. Slavskii, I.A. Kuznetsov, T.I. Shashkova, G.A. Bazykin, T.I. Axenovich,
    F. Kondrashov, Y.S. Aulchenko, European Journal of Human Genetics 29 (2021) 1082–1091.
date_created: 2021-08-15T22:01:28Z
date_published: 2021-07-01T00:00:00Z
date_updated: 2025-07-10T12:02:05Z
day: '01'
ddc:
- '576'
department:
- _id: FyKo
doi: 10.1038/s41431-021-00836-7
ec_funded: 1
external_id:
  isi:
  - '000625853200001'
  pmid:
  - '33664501'
file:
- access_level: open_access
  checksum: a676d76f91b0dbe0504c63e469129c2a
  content_type: application/pdf
  creator: asandaue
  date_created: 2021-08-16T09:14:36Z
  date_updated: 2021-08-16T09:14:36Z
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  file_size: 1079395
  relation: main_file
  success: 1
file_date_updated: 2021-08-16T09:14:36Z
has_accepted_license: '1'
intvolume: '        29'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1082-1091
pmid: 1
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '771209'
  name: Characterizing the fitness landscape on population and global scales
publication: European Journal of Human Genetics
publication_identifier:
  eissn:
  - 1476-5438
  issn:
  - 1018-4813
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: The limits of normal approximation for adult height
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 29
year: '2021'
...