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Simulations and directed acyclic graphs explained why assortative mating biases the prenatal negative control design

Madley-Dowd, Paul, Rai, Dheeraj, Zammit, Stanley and Heron, Jon 2020. Simulations and directed acyclic graphs explained why assortative mating biases the prenatal negative control design. Journal of Clinical Epidemiology 118 , pp. 9-17. 10.1016/j.jclinepi.2019.10.008

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Objective The negative control design can be used to provide evidence for whether a prenatal exposure-outcome association occurs by in-utero mechanisms. Assortative mating has been suggested to influence results from negative control designs, though how and why has not yet been adequately explained. We aimed to explain why mutual adjustment of maternal and paternal exposure in regression models can account for assortative mating. Study design and setting We used directed acyclic graphs to show how bias can occur when modelling maternal and paternal effects separately. We empirically tested our claims using a simulation study. We investigated how increasing assortative mating influences the bias of effect estimates obtained from models that do and do not use a mutual adjustment strategy. Results In models without mutual adjustment, increasing assortative mating lead to increasing bias in effect estimates. The maternal and paternal effect estimates were biased by each other, making the difference between them smaller than the true difference. Mutually adjusted models did not suffer from such bias. Conclusions Mutual adjustment for maternal and paternal exposure prevents bias from assortative mating influencing the conclusions of a negative control design. We further discuss issues that mutual adjustment may not be able to resolve.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0895-4356
Date of First Compliant Deposit: 13 November 2019
Date of Acceptance: 29 October 2019
Last Modified: 28 Nov 2020 00:05

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