1. Epidemiology and Global Health

Risk factors relate to the variability of health outcomes as well as the mean: a GAMLSS tutorial

  1. David Bann  Is a corresponding author
  2. Liam Wright
  3. Tim J Cole
  1. University College London, United Kingdom
https://doi.org/10.7554/eLife.72357
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  1. David Bann
  2. Liam Wright
  3. Tim J Cole
(2022)
Risk factors relate to the variability of health outcomes as well as the mean: a GAMLSS tutorial
eLife 11:e72357.
https://doi.org/10.7554/eLife.72357
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Abstract

Background: Risk factors or interventions may affect the variability as well as the mean of health outcomes. Understanding this can aid aetiological understanding and public health translation, in that interventions which shift the outcome mean and reduce variability are typically preferable to those which affect only the mean. However, most commonly used statistical tools do not test for differences in variability. Tools that do have few epidemiological applications to date, and fewer applications still have attempted to explain their resulting findings. We thus provide a tutorial for investigating this using GAMLSS (Generalised Additive Models for Location, Scale and Shape).

Methods: The 1970 British birth cohort study was used, with body mass index (BMI; N=6,007) and mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; N=7,104) measured in midlife (42-46 years) as outcomes. We used GAMLSS to investigate how multiple risk factors (sex, childhood social class and midlife physical inactivity) related to differences in health outcome mean and variability.

Results: Risk factors were related to sizable differences in outcome variability-for example males had marginally higher mean BMI yet 28% lower variability; lower social class and physical inactivity were each associated with higher mean and higher variability (6.1% and 13.5% higher variability, respectively). For mental wellbeing, gender was not associated with the mean while males had lower variability (-3.9%); lower social class and physical inactivity were each associated with lower mean yet higher variability (7.2% and 10.9% higher variability, respectively).

Conclusions: The results highlight how GAMLSS can be used to investigate how risk factors or interventions may influence the variability in health outcomes. This underutilised approach to the analysis of continuously distributed outcomes may have broader utility in epidemiologic, medical, and psychological sciences. A tutorial and replication syntax is provided online to facilitate this (https://osf.io/5tvz6/).

Funding: DB is supported by the Economic and Social Research Council (grant number ES/M001660/1), The Academy of Medical Sciences / Wellcome Trust ('Springboard Health of the Public in 2040' award: HOP001/1025); DB and LW are supported by the Medical Research Council (MR/V002147/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data availability

All data are available to download from the UK Data Archive: https://beta.ukdataservice.ac.uk/datacatalogue/series/series?id=200001

Article and author information

Author details

  1. David Bann

    Centre for Longitudinal Studies, Social Research Institute, University College London, london, United Kingdom
    For correspondence
    david.bann@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6454-626X

  2. Liam Wright

    Centre for Longitudinal Studies, Social Research Institute, University College London, london, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Tim J Cole

    Great Ormond Street Institute of Child Health, University College London, london, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Medical Research Council (MR/V002147/1)

  • David Bann
  • Liam Wright

Economic and Social Research Council (ES/M001660/1)

  • Liam Wright

Wellcome Trust (HOP001/1025)

  • David Bann

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 paper uses secondary data analysis using data from a cohort study which has been followed-up since birth in 1970. Cohort members provided informed consent, and the study received full ethical approval - most recently from the NRES Committee South East Coast-Brighton and Sussex.

Reviewing Editor

  1. Belinda Nicolau, McGill University, Canada

Version history

  1. Preprint posted: March 31, 2021 (view preprint)
  2. Received: July 20, 2021
  3. Accepted: January 4, 2022
  4. Accepted Manuscript published: January 5, 2022 (version 1)
  5. Version of Record published: January 26, 2022 (version 2)

Copyright

© 2022, Bann 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. David Bann
  2. Liam Wright
  3. Tim J Cole
(2022)
Risk factors relate to the variability of health outcomes as well as the mean: a GAMLSS tutorial
eLife 11:e72357.
https://doi.org/10.7554/eLife.72357

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Further reading

    1. Epidemiology and Global Health
    2. Medicine

    Association between bisphosphonate use and COVID-19 related outcomes

    Jeffrey Thompson, Yidi Wang ... Ulrich H von Andrian
    Research Article Updated

    Background:

    Although there are several efficacious vaccines against COVID-19, vaccination rates in many regions around the world remain insufficient to prevent continued high disease burden and emergence of viral variants. Repurposing of existing therapeutics that prevent or mitigate severe COVID-19 could help to address these challenges. The objective of this study was to determine whether prior use of bisphosphonates is associated with reduced incidence and/or severity of COVID-19.

    Methods:

    A retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance January 1, 2019 to June 30, 2020 was performed. The primary exposure of interest was use of any bisphosphonate from January 1, 2019 to February 29, 2020. Bisphosphonate users were identified as patients having at least one bisphosphonate claim during this period, who were then 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Main outcomes of interest included: (a) any testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with a COVID-19 diagnosis between March 1, 2020 and June 30, 2020. Multiple sensitivity analyses were also performed to assess core study outcomes amongst more restrictive matches between BP users/non-users, as well as assessing the relationship between BP-use and other respiratory infections (pneumonia, acute bronchitis) both during the same study period as well as before the COVID outbreak.

    Results:

    A total of 7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. A total of 450,366 bisphosphonate users were identified and 1:1 propensity score-matched to bisphosphonate non-users. Bisphosphonate users had lower odds ratios (OR) of testing for SARS-CoV-2 infection (OR = 0.22; 95%CI:0.21–0.23; p<0.001), COVID-19 diagnosis (OR = 0.23; 95%CI:0.22–0.24; p<0.001), and COVID-19-related hospitalization (OR = 0.26; 95%CI:0.24–0.29; p<0.001). Sensitivity analyses yielded results consistent with the primary analysis. Bisphosphonate-use was also associated with decreased odds of acute bronchitis (OR = 0.23; 95%CI:0.22–0.23; p<0.001) or pneumonia (OR = 0.32; 95%CI:0.31–0.34; p<0.001) in 2019, suggesting that bisphosphonates may protect against respiratory infections by a variety of pathogens, including but not limited to SARS-CoV-2.

    Conclusions:

    Prior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes.

    Funding:

    This study was supported by NIH grants, AR068383 and AI155865, a grant from MassCPR (to UHvA) and a CRI Irvington postdoctoral fellowship, CRI2453 (to PH).

    1. Epidemiology and Global Health

    Sleep: Another benefit of regular sleep

    Tianyi Huang
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    A large observational study has found that irregular sleep-wake patterns are associated with a higher risk of overall mortality, and also mortality from cancers and cardiovascular disease.

    1. Epidemiology and Global Health

    Sleep regularity and mortality: a prospective analysis in the UK Biobank

    Lachlan Cribb, Ramon Sha ... Matthew P Pase
    Research Article

    Background:

    Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort.

    Methods:

    The sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hr apart, averaged over 7 days of accelerometry (range 0–100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models.

    Results:

    The mean sample age was 62 years (standard deviation [SD], 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p [global test of spline term]<0.001). Hazard ratios, relative to the median SRI, were 1.53 (95% confidence interval [CI]: 1.41, 1.66) for participants with SRI at the 5th percentile (SRI = 41) and 0.90 (95% CI: 0.81, 1.00) for those with SRI at the 95th percentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern.

    Conclusions:

    Irregular sleep-wake patterns are associated with higher mortality risk.

    Funding:

    National Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer’s Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).