Identifying Multi-Omics Causers and Causal Pathways for Complex Traits.
Front Genet
; 10: 110, 2019.
Article
em En
| MEDLINE
| ID: mdl-30847004
ABSTRACT
The central dogma of molecular biology delineates a unidirectional causal flow, i.e., DNA â RNA â protein â trait. Genome-wide association studies, next-generation sequencing association studies, and their meta-analyses have successfully identified ~12,000 susceptibility genetic variants that are associated with a broad array of human physiological traits. However, such conventional association studies ignore the mediate causers (i.e., RNA, protein) and the unidirectional causal pathway. Such studies may not be ideally powerful; and the genetic variants identified may not necessarily be genuine causal variants. In this article, we model the central dogma by a mediate causal model and analytically prove that the more remote an omics level is from a physiological trait, the smaller the magnitude of their correlation is. Under both random and extreme sampling schemes, we numerically demonstrate that the proteome-trait correlation test is more powerful than the transcriptome-trait correlation test, which in turn is more powerful than the genotype-trait association test. In conclusion, integrating RNA and protein expressions with DNA data and causal inference are necessary to gain a full understanding of how genetic causal variants contribute to phenotype variations.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
Front Genet
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos