Causal inference in genetic trio studies

DOI10.1073/PNAS.2007743117zbMATH Open1485.92072arXiv2002.09644OpenAlexW3087137395WikidataQ99571954 ScholiaQ99571954MaRDI QIDQ5073167FDOQ5073167

Authors: Stephen Bates, Matteo Sesia, Emmanuel J. Candès 

Publication date: 5 May 2022

Published in: Proceedings of the National Academy of Sciences (Search for Journal in Brave)

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.

Full work available at URL: https://arxiv.org/abs/2002.09644

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Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Genetics and epigenetics (92D10) Causal inference from observational studies (62D20)

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Cited In (10)

• On the power of conditional independence testing under model-X
• Discussion of the Paper “Prediction, Estimation, and Attribution” by B. Efron
• Reconciling model-X and doubly robust approaches to conditional independence testing
• Relationship inference from the genetic data on parents or offspring: a comparative study
• What is a Randomization Test?
• Hypothesis testing in adaptively sampled data: ART to maximize power beyond \textit{iid }sampling
• 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
• Learning to increase the power of conditional randomization tests

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