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Survival Bias in Mendelian Randomization Studies: A Threat to Causal Inference

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  • Roelof A.J. Smit, Department of Human Genetics, Leiden University Medical Center (LUMC).
  • ,
  • Stella Trompet, Department of Human Genetics, Leiden University Medical Center (LUMC).
  • ,
  • Olaf M. Dekkers
  • J. Wouter Jukema, Department of Human Genetics, Leiden University Medical Center (LUMC).
  • ,
  • Saskia le Cessie, Department of Human Genetics, Leiden University Medical Center (LUMC).

It has been argued that survival bias may distort results in Mendelian randomization studies in older populations. Through simulations of a simple causal structure we investigate the degree to which instrumental variable (IV)-estimators may become biased in the context of exposures that affect survival. We observed that selecting on survival decreased instrument strength and, for exposures with directionally concordant effects on survival (and outcome), introduced downward bias of the IV-estimator when the exposures reduced the probability of survival till study inclusion. Higher ages at study inclusion generally increased this bias, particularly when the true causal effect was not equal to null. Moreover, the bias in the estimated exposure-outcome relation depended on whether the estimation was conducted in the one- or two-sample setting. Finally, we briefly discuss which statistical approaches might help to alleviate this and other types of selection bias. See video abstract at, http://links.lww.com/EDE/B589.

Original languageEnglish
JournalEpidemiology
Volume30
Issue6
Pages (from-to)813-816
Number of pages4
ISSN1044-3983
DOIs
Publication statusPublished - Nov 2019

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