Sonja A. Find articles by Sonja A. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence: Elizabeth W.
E-mail: ln. Received Oct 3; Accepted Oct 2. Published by Wolters Kluwer Health, Inc. The work cannot be changed in any way or used commercially without permission from the journal. This article has been cited by other articles in PMC.
Background: Investigators often support the validity of Mendelian randomization MR studies, an instrumental variable approach proposing genetic variants as instruments, via. Methods: We applied the instrumental inequalities to an MR analysis of the effect of maternal pregnancy vitamin D on offspring psychiatric outcomes, proposing four independent maternal genetic variants as instruments. Results: The instrumental inequalities were satisfied i. Conclusions: The instrumental inequalities detected violations of the MR assumptions for genetic variants jointly proposed as instruments in our study, although the instrumental inequalities were satisfied when considering each proposed instrument separately.
Keywords: Falsification, Instrumental inequalities, Instrumental variable, Mendelian randomization. Briefly, a valid MR analysis with one genetic variant requires: 1 The genetic variant Z is associated with the exposure X 2 The genetic variant Z does not affect the outcome Y except through its effect on the exposure X 3 Individuals at different levels of the genetic variant Z are exchangeable i.
Open in a separate window. Exposure Pregnancy serum vitamin D status was defined using the storage form of vitamin D, total 25OHD, measured in venous blood taken between Analysis We assessed whether the instrumental inequalities would identify violations of MR models for the causal effect of maternal serum vitamin D during pregnancy on offspring PDP and ADHD symptoms, using the above-mentioned four SNPs proposed as instruments. Results For all definitions of exposures and outcomes, the instrumental inequalities, including the stronger inequalities developed by Bonet 15 , held for each SNP individually, indicating that there was no evidence in the data alone against each specific proposed instrument being valid.
TABLE 1. TABLE 3. TABLE 2. Supplementary Material Click here to view. Footnotes This project is supported by an innovation program under the Marie Sklodowska-Curie grant agreement number Causal Inference: What If. Robins JM. The analysis of randomized and non-randomized AIDS treatment trials using a new approach to causal inference in longitudinal studies.
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Vitamin D and risk of multiple sclerosis: a Mendelian randomization study. PLoS Med. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. D A day with no glory A heart filled with fear Still repeati… P. A day with no glory A heart filled with fear Still repeating… P.
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