Causal inference in genetic trio studies.
Proc Natl Acad Sci U S A
; 117(39): 24117-24126, 2020 09 29.
Article
em En
| MEDLINE
| ID: mdl-32948695
ABSTRACT
We introduce a method to 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 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 to determine statistical significance, and it can leverage any black-box multivariate model and additional nontrio genetic data to increase power. Crucially, our inferences are based only on a well-established mathematical model of recombination and make no assumptions about the relationship between the genotypes and phenotypes. We compare our method to the widely used transmission disequilibrium test and demonstrate enhanced power and localization.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Variação Genética
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Técnicas Genéticas
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Hereditariedade
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Estudos de Associação Genética
Tipo de estudo:
Clinical_trials
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Evaluation_studies
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2020
Tipo de documento:
Article