A Robust Method Uncovers Significant Context-Specific Heritability in Diverse Complex Traits.
Am J Hum Genet
; 106(1): 71-91, 2020 01 02.
Article
en En
| MEDLINE
| ID: mdl-31901249
ABSTRACT
Gene-environment interactions (GxE) can be fundamental in applications ranging from functional genomics to precision medicine and is a conjectured source of substantial heritability. However, unbiased methods to profile GxE genome-wide are nascent and, as we show, cannot accommodate general environment variables, modest sample sizes, heterogeneous noise, and binary traits. To address this gap, we propose a simple, unifying mixed model for gene-environment interaction (GxEMM). In simulations and theory, we show that GxEMM can dramatically improve estimates and eliminate false positives when the assumptions of existing methods fail. We apply GxEMM to a range of human and model organism datasets and find broad evidence of context-specific genetic effects, including GxSex, GxAdversity, and GxDisease interactions across thousands of clinical and molecular phenotypes. Overall, GxEMM is broadly applicable for testing and quantifying polygenic interactions, which can be useful for explaining heritability and invaluable for determining biologically relevant environments.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Marcadores Genéticos
/
Herencia Multifactorial
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Interacción Gen-Ambiente
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Trastornos Mentales
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Modelos Genéticos
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Hum Genet
Año:
2020
Tipo del documento:
Article