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Estimating the causal effects of modifiable, non-genetic factors on Huntington Disease progression using propensity score weighting

Griffin, Bethan Ann, Suttorp, Marika, Busse, Monica, Wild, Edward J, Setodji, Claude, Warner, John H., Sampaio, Christina and Mohan, Amrita 2021. Estimating the causal effects of modifiable, non-genetic factors on Huntington Disease progression using propensity score weighting. Parkinsonism and Related Disorders 83 , pp. 56-62. 10.1016/j.parkreldis.2021.01.010

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Introduction Despite being genetically inherited, it is unclear how non-genetic factors (e.g., substance use, employment) might contribute to the progression and severity of Huntington's disease (HD). Methods We used propensity score (PS) weighting in a large (n = 2914) longitudinal dataset (Enroll-HD) to examine the impact of education, employment status, and use of tobacco, alcohol, and recreational and therapeutic drugs on HD progression. Each factor was investigated in isolation while controlling for 19 other factors to ensure that groups were balanced at baseline on potential confounders using PS weights. Outcomes were compared several years later using doubly robust models. Results Our results highlighted cases where modifiable (non-genetic) factors - namely light and moderate alcohol use and employment - would have been associated with HD progression in models that did not use PS weights to control for baseline imbalances. These associations did not hold once we applied PS weights to balance baseline groups. We also found potential evidence of a protective effect of substance use (primarily marijuana use), and that those who needed antidepressant treatment were likely to progress faster than non-users. Conclusions Our study is the first to examine the effect of non-genetic factors on HD using a novel application of PS weighting. We show that previously-reported associated factors – including light and moderate alcohol use – are reduced and no longer significantly linked to HD progression after PS weighting. This indicates the potential value of PS weighting in examining non-genetic factors contributing to HD as well as in addressing the known biases that occur with observational data.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: Elsevier
ISSN: 1353-8020
Date of First Compliant Deposit: 13 January 2021
Date of Acceptance: 10 January 2021
Last Modified: 13 Jan 2022 16:48

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