Efficient Integrative Multi-SNP Association Analysis via Deterministic Approximation of Posteriors.
Am J Hum Genet
; 98(6): 1114-1129, 2016 06 02.
Article
em En
| MEDLINE
| ID: mdl-27236919
ABSTRACT
With the increasing availability of functional genomic data, incorporating genomic annotations into genetic association analysis has become a standard procedure. However, the existing methods often lack rigor and/or computational efficiency and consequently do not maximize the utility of functional annotations. In this paper, we propose a rigorous inference procedure to perform integrative association analysis incorporating genomic annotations for both traditional GWASs and emerging molecular QTL mapping studies. In particular, we propose an algorithm, named deterministic approximation of posteriors (DAP), which enables highly efficient and accurate joint enrichment analysis and identification of multiple causal variants. We use a series of simulation studies to highlight the power and computational efficiency of our proposed approach and further demonstrate it by analyzing the cross-population eQTL data from the GEUVADIS project and the multi-tissue eQTL data from the GTEx project. In particular, we find that genetic variants predicted to disrupt transcription factor binding sites are enriched in cis-eQTLs across all tissues. Moreover, the enrichment estimates obtained across the tissues are correlated with the cell types for which the annotations are derived.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
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Polimorfismo de Nucleotídeo Único
/
Genômica
/
Locos de Características Quantitativas
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Biologia de Sistemas
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Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2016
Tipo de documento:
Article