Taller height and risk of coronary heart disease and cancer, a within-sibship Mendelian randomization study

  1. Laurence J Howe  Is a corresponding author
  2. Ben Brumpton
  3. Humaira Rasheed
  4. Bjørn Olav Åsvold
  5. George Davey Smith
  6. Neil Martin Davies  Is a corresponding author
  1. University of Bristol, United Kingdom
  2. Norwegian University of Science and Technology, Norway

Abstract

Background: Taller people have lower risk of coronary heart disease but higher risk of many cancers. Mendelian randomization (MR) studies in unrelated individuals (population MR) have suggested that these relationships are potentially causal. However, population MR studies are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects.

Methods: In this study, we performed within-sibship MR analyses using 78,988 siblings, a design robust against demography and indirect genetic effects of parents. For comparison we also applied population MR and estimated associations with measured height.

Results: Within-sibship Mendelian randomization estimated that one SD taller height lowers odds of coronary heart disease by 14% (95% CI: 3% to 23%) but increases odds of cancer by 18% (95% CI: 3% to 34%), highly consistent with population MR and height-disease association estimates. There was some evidence that taller height reduces systolic blood pressure and LDL cholesterol, which may mediate some of the protective effect of taller height on coronary heart disease risk.

Conclusions: For the first time, we have demonstrated that purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve understanding of the aetiologies of atherosclerosis and carcinogenesis.

Funding: This project was conducted by researchers at the MRC Integrative Epidemiology Unit [MC_UU_00011/1] and also supported by a Norwegian Research Council Grant number 295989.

Data availability

We used individual level data from the UK Biobank and HUNT cohorts. Participants in these studies have consented to the use of their data in medical research and so these data are not publicly available. Data access can be applied for by qualified researchers.For access to UK Biobank individual level participant data, please send enquiries to access@ukbiobank.ac.uk and see information on the UK Biobank website http://www.ukbiobank.ac.uk. UK Biobank access generally involves submitting project proposals which are evaluated by the study data access committee.Researchers associated with Norwegian research institutes can apply for the use of HUNT data and samples with approval by the Regional Committee for Medical and Health Research Ethics. HUNT data is governed by Norwegian law, therefore researchers from other countries may apply if collaborating with a Norwegian Principal Investigator. Detailed information on the data access procedure of HUNT can be found at https://www.ntnu.edu/hunt/data.Statistical code for population and within-sibship models used in the manuscript is available on GitHub https://github.com/LaurenceHowe/WithinSibshipModels/

Article and author information

Author details

  1. Laurence J Howe

    Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
    For correspondence
    lh14833@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2819-9686
  2. Ben Brumpton

    Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  3. Humaira Rasheed

    Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3331-5864
  4. Bjørn Olav Åsvold

    Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  5. George Davey Smith

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1407-8314
  6. Neil Martin Davies

    Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
    For correspondence
    neil.davies@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2460-0508

Funding

Norwegian Research Council (295989)

  • Neil Martin Davies

Medical Research Council (00011/1)

  • George Davey Smith

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This research has been conducted using the UK Biobank Resource under Application Number 15825. UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee (MREC). All UK Biobank participants provided written informed consent. The use of HUNT data in this study was approved by the Regional Committee for Ethics in Medical Research, Central Norway (2017/2479). All HUNT study participants provided written informed consent.

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

Publication history

  1. Preprint posted: July 19, 2021 (view preprint)
  2. Received: August 11, 2021
  3. Accepted: March 9, 2022
  4. Accepted Manuscript published: March 18, 2022 (version 1)
  5. Version of Record published: March 24, 2022 (version 2)

Copyright

© 2022, Howe et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Laurence J Howe
  2. Ben Brumpton
  3. Humaira Rasheed
  4. Bjørn Olav Åsvold
  5. George Davey Smith
  6. Neil Martin Davies
(2022)
Taller height and risk of coronary heart disease and cancer, a within-sibship Mendelian randomization study
eLife 11:e72984.
https://doi.org/10.7554/eLife.72984

Further reading

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    Denmark was one of the few countries where it was politically decided to continue cancer screening during the COVID-19 pandemic. We assessed the actual population uptake of mammography and cervical screening during this period.

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    Denmark continued cancer screening during the pandemic, but following the first lockdown a temporary drop was seen in breast and cervical screening activity.

    Funding:

    Region Zealand (R22-A597).

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