MR-DoC2: Bidirectional Causal Modeling with Instrumental Variables and Data from Relatives

Luis F.S. Castro-de-Araujo*, Madhurbain Singh, Yi Zhou, Philip Vinh, Brad Verhulst, Conor V. Dolan, Michael C. Neale

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Establishing causality is an essential step towards developing interventions for psychiatric disorders, substance use and many other conditions. While randomized controlled trials (RCTs) are considered the gold standard for causal inference, they are unethical in many scenarios. Mendelian randomization (MR) can be used in such cases, but importantly both RCTs and MR assume unidirectional causality. In this paper, we developed a new model, MRDoC2, that can be used to identify bidirectional causation in the presence of confounding due to both familial and non-familial sources. Our model extends the MRDoC model (Minică et al. in Behav Genet 48:337–349, https://doi.org/10.1007/s10519-018-9904-4, 2018), by simultaneously including risk scores for each trait. Furthermore, the power to detect causal effects in MRDoC2 does not require the phenotypes to have different additive genetic or shared environmental sources of variance, as is the case in the direction of causation twin model (Heath et al. in Behav Genet 23:29–50, https://doi.org/10.1007/BF01067552, 1993).

Original languageEnglish
Pages (from-to)63-73
Number of pages11
JournalBehavior Genetics
Volume53
Issue number1
Early online date2 Nov 2022
DOIs
Publication statusPublished - Feb 2023

Bibliographical note

Funding Information:
LFSCA is funded by NIH Grant No. 5T32MH-020030 and the Medical Research Council - UK, Grant No. MR/T03355X/1 during the study. MCN was funded by NIH Grant DA-049867.

Publisher Copyright:
© 2022, The Author(s).

Funding

LFSCA is funded by NIH Grant No. 5T32MH-020030 and the Medical Research Council - UK, Grant No. MR/T03355X/1 during the study. MCN was funded by NIH Grant DA-049867.

FundersFunder number
National Institutes of Health5T32MH-020030
Foundation for the National Institutes of Health
Medical Research CouncilMR/T03355X/1, DA-049867

    Keywords

    • Causality
    • Mendelian randomization
    • Pleiotropy
    • Twin design

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