Taller height and risk of coronary heart disease and cancer, a within-sibship Mendelian randomization study
- University of Bristol, United Kingdom
- 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
George Davey Smith
Neil Martin Davies
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
- Edward D Janus, University of Melbourne, Australia
Publication history
- Preprint posted: July 19, 2021 (view preprint)
- Received: August 11, 2021
- Accepted: March 9, 2022
- Accepted Manuscript published: March 18, 2022 (version 1)
- 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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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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- Epidemiology and Global Health
Background:
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.
Methods:
The first COVID-19 lockdown in Denmark was announced on 11 March 2020. To investigate possible changes in cancer screening activity due to the COVID-19 pandemic, we analysed data from the beginning of 2017 until the end of 2021. A time series analysis was carried out to discover possible trends and outliers in the screening activities in the period 2017–2021. Data on mammography screening and cervical screening were retrieved from governmental pandemic-specific monitoring of health care activities.
Results:
A brief drop was seen in screening activity right after the first COVID-19 lockdown, but the activity quickly returned to its previous level. A short-term deficit of 43% [CI –49 to –37] was found for mammography screening. A short-term deficit of 62% [CI –65 to –58] was found for cervical screening. Furthermore, a slight, statistically significant downward trend in cervical screening from 2018 to 2021 was probably unrelated to the pandemic. Other changes, for example, a marked drop in mammography screening towards the end of 2021, also seem unrelated to the pandemic.
Conclusions:
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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- Epidemiology and Global Health
To curb the initial spread of SARS-CoV-2, many countries relied on nation-wide implementation of non-pharmaceutical intervention measures, resulting in substantial socio-economic impacts. Potentially, subnational implementations might have had less of a societal impact, but comparable epidemiological impact. Here, using the first COVID-19 wave in the Netherlands as a case in point, we address this issue by developing a high-resolution analysis framework that uses a demographically stratified population and a spatially explicit, dynamic, individual contact-pattern based epidemiology, calibrated to hospital admissions data and mobility trends extracted from mobile phone signals and Google. We demonstrate how a subnational approach could achieve similar level of epidemiological control in terms of hospital admissions, while some parts of the country could stay open for a longer period. Our framework is exportable to other countries and settings, and may be used to develop policies on subnational approach as a better strategic choice for controlling future epidemics.
