Causal inference in genetic trio studies
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Publication:5073167
Abstract: We introduce a method to rigorously draw causal inferences---inferences immune to all possible confounding---from genetic data that include parents and offspring. Causal conclusions are possible with these data because the natural randomness in meiosis can be viewed as a high-dimensional randomized experiment. We make this observation actionable by developing a novel conditional independence test that identifies regions of the genome containing distinct causal variants. The proposed Digital Twin Test compares an observed offspring to carefully constructed synthetic offspring from the same parents in order to determine statistical significance, and it can leverage any black-box multivariate model and additional non-trio genetic data in order to increase power. Crucially, our inferences are based only on a well-established mathematical description of the rearrangement of genetic material during meiosis and make no assumptions about the relationship between the genotypes and phenotypes.
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Cites work
- scientific article; zbMATH DE number 720689 (Why is no real title available?)
- scientific article; zbMATH DE number 6122810 (Why is no real title available?)
- 10.1162/153244303321897717
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Cited in
(10)- Learning to increase the power of conditional randomization tests
- On the power of conditional independence testing under model-X
- Discussion of the Paper “Prediction, Estimation, and Attribution” by B. Efron
- Relationship inference from the genetic data on parents or offspring: a comparative study
- Reconciling model-X and doubly robust approaches to conditional independence testing
- Hypothesis testing in adaptively sampled data: ART to maximize power beyond \textit{iid }sampling
- What is a Randomization Test?
- Double Empirical Bayes Testing
- Causal graphical models in systems genetics: a unified framework for joint inference of causal network and genetic architecture for correlated phenotypes
- New perspectives on knockoffs construction
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