eprintid: 10171019
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/17/10/19
datestamp: 2023-06-01 09:36:09
lastmod: 2023-06-01 09:36:09
status_changed: 2023-06-01 09:36:09
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Morris, Tim T
creators_name: Heron, Jon
creators_name: Sanderson, Eleanor CM
creators_name: Davey Smith, George
creators_name: Didelez, Vanessa
creators_name: Tilling, Kate
title: Interpretation of Mendelian randomization using a single measure of an exposure that varies over time
ispublished: pub
divisions: UCL
divisions: B16
divisions: B14
divisions: J81
divisions: K26
keywords: Science & Technology, Life Sciences & Biomedicine, Public, Environmental & Occupational Health, Mendelian randomization, causal inference, longitudinal, simulation, BLOOD-PRESSURE, EARLY-LIFE, GENE, VARIANTS, AGE
note: © The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
abstract: Background: Mendelian randomization (MR) is a powerful tool through which the causal effects of modifiable exposures on outcomes can be estimated from observational data. Most exposures vary throughout the life course, but MR is commonly applied to one measurement of an exposure (e.g. weight measured once between ages 40 and 60 years). It has been argued that MR provides biased causal effect estimates when applied to one measure of an exposure that varies over time. Methods: We propose an approach that emphasizes the liability that causes the entire exposure trajectory. We demonstrate this approach using simulations and an applied example. Results: We show that rather than estimating the direct or total causal effect of changing the exposure value at a given time, MR estimates the causal effect of changing the underlying liability for the exposure, scaled to the effect of the liability on the exposure at that time. As such, results from MR conducted at different time points are expected to differ (unless the effect of the liability on exposure is constant over time), as we illustrate by estimating the effect of body mass index measured at different ages on systolic blood pressure. Conclusion: Univariable MR results should not be interpreted as time-point-specific direct or total causal effects, but as the effect of changing the liability for the exposure. Estimates of how the effects of a genetic variant on an exposure vary over time, together with biological knowledge that provides evidence regarding likely effective exposure periods, are required to interpret time-point-specific causal effects.
date: 2022-12
date_type: published
publisher: OXFORD UNIV PRESS
official_url: https://doi.org/10.1093/ije/dyac136
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1998451
doi: 10.1093/ije/dyac136
medium: Print
pii: 6645008
lyricists_name: Morris, Tim
lyricists_id: TMORR75
actors_name: Morris, Tim
actors_id: TMORR75
actors_role: owner
funding_acknowledgements: MC_UU_00011/1 [UK Medical Research Council]; MC_UU_00011/3 [UK Medical Research Council]
full_text_status: public
publication: International Journal of Epidemiology
volume: 51
number: 6
pagerange: 1899-1909
pages: 11
event_location: England
issn: 0300-5771
citation:        Morris, Tim T;    Heron, Jon;    Sanderson, Eleanor CM;    Davey Smith, George;    Didelez, Vanessa;    Tilling, Kate;      (2022)    Interpretation of Mendelian randomization using a single measure of an exposure that varies over time.                   International Journal of Epidemiology , 51  (6)   pp. 1899-1909.    10.1093/ije/dyac136 <https://doi.org/10.1093/ije%2Fdyac136>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10171019/1/Interpretation%20of%20Mendelian%20randomization%20using%20a%20single%20measure%20of%20an%20exposure%20that%20varies%20over%20time.pdf