Using allele scores to identify confounding by reverse causation: studies of alcohol consumption as an exemplar

Hannah M. Sallis; Tom Palmer; Kate Tilling; George Davey Smith; Marcus R. Munafò

doi:10.1093/ije/dyac165

Using allele scores to identify confounding by reverse causation: studies of alcohol consumption as an exemplar

Hannah M. Sallis, Tom Palmer, Kate Tilling, George Davey Smith, Marcus R. Munafò

Vice Chancellor's Office

Research output: Contribution to journal › Article › peer-review

4 Citations (SciVal)

Abstract

Background: Mendelian randomization (MR) is a form of instrumental variable analysis used to investigate causality using observational data. Another important, although less frequently applied, use of this technique is to investigate confounding due to reverse causality.

Methods: We used a form of reverse MR and data from UK Biobank in a proof-of-principle study to investigate confounding due to reverse causation. Here we focus on the association between alcohol consumption (exposure) and outcomes including educational attainment, and physical and mental health. First, we examined the observational relationship between alcohol consumption and these outcomes. Allele scores were then derived for educational attainment, and physical and mental health, and the association with alcohol consumption (as the outcome) was explored. Sample sizes ranged from 114 941–336 473 in observational analyses and 142 093–336 818 in genetic analyses.

Results: Conventional observational analyses indicated associations between alcohol consumption and a number of outcomes (e.g. neuroticism, body mass index, educational attainment). Analyses using allele scores suggested evidence of reverse causation for several of these relationships (in particular physical health and educational attainment).

Conclusion: Allele scores allow us to investigate reverse causation in observational studies. Our findings suggest that observed associations implying beneficial effects of alcohol consumption may be due to confounding by reverse causation in many cases.

Original language	English
Pages (from-to)	536-544
Number of pages	9
Journal	International Journal of Epidemiology
Volume	52
Issue number	2
Early online date	18 Aug 2022
DOIs	https://doi.org/10.1093/ije/dyac165
Publication status	Published - 1 Apr 2023

Data Availability Statement

The UK Biobank data set used to conduct the research in this paper is available via application directly to UK Biobank. Applications are assessed for meeting the required criteria for access, including legal and ethics standards. More information regarding data access can be found at http://www.ukbiobank.ac.uk/scientists-3/.

Acknowledgements

This research has been conducted using the UK Biobank resource under application number 9142.

Funding

This work was supported by the Medical Research Council and the University of Bristol (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/7) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol.

Keywords

allele scores
confounding
Mendelian randomization
Reverse causation

ASJC Scopus subject areas

Epidemiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ije/dyac165Licence: CC BY

Cite this

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abstract = "Background: Mendelian randomization (MR) is a form of instrumental variable analysis used to investigate causality using observational data. Another important, although less frequently applied, use of this technique is to investigate confounding due to reverse causality. Methods: We used a form of reverse MR and data from UK Biobank in a proof-of-principle study to investigate confounding due to reverse causation. Here we focus on the association between alcohol consumption (exposure) and outcomes including educational attainment, and physical and mental health. First, we examined the observational relationship between alcohol consumption and these outcomes. Allele scores were then derived for educational attainment, and physical and mental health, and the association with alcohol consumption (as the outcome) was explored. Sample sizes ranged from 114 941–336 473 in observational analyses and 142 093–336 818 in genetic analyses. Results: Conventional observational analyses indicated associations between alcohol consumption and a number of outcomes (e.g. neuroticism, body mass index, educational attainment). Analyses using allele scores suggested evidence of reverse causation for several of these relationships (in particular physical health and educational attainment). Conclusion: Allele scores allow us to investigate reverse causation in observational studies. Our findings suggest that observed associations implying beneficial effects of alcohol consumption may be due to confounding by reverse causation in many cases.",

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Using allele scores to identify confounding by reverse causation: studies of alcohol consumption as an exemplar

Abstract

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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