scholarly journals Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for theCYP4F3locus

2017 ◽  
Vol 56 (6) ◽  
pp. 1663-1672 ◽  
Author(s):  
Jieyun Yin ◽  
Hongliang Liu ◽  
Zhensheng Liu ◽  
Kouros Owzar ◽  
Younghun Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pathway Analysis ◽  
Potential Role ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

A Bayesian Hierarchical Framework for Pathway Analysis in Genome-Wide Association Studies

2019 ◽  
Vol 84 (6) ◽  
pp. 240-255
Author(s):  
Lei Zhang ◽  
Charalampos Papachristou ◽  
Pankaj K. Choudhary ◽  
Swati Biswas
Keyword(s):  
Pathway Analysis ◽  
Ad Hoc ◽  
Association Studies ◽  
Weighted Least Squares ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Model Framework ◽  
Bayesian Hierarchical ◽  
Genome Wide ◽  
Joint Consideration

<b><i>Background:</i></b> Pathway analysis allows joint consideration of multiple SNPs belonging to multiple genes, which in turn belong to a biologically defined pathway. This type of analysis is usually more powerful than single-SNP analyses for detecting joint effects of variants in a pathway. <b><i>Methods:</i></b> We develop a Bayesian hierarchical model by fully modeling the 3-level hierarchy, namely, SNP-gene-pathway that is naturally inherent in the structure of the pathways, unlike the currently used ad hoc ways of combining such information. We model the effects at each level conditional on the effects of the levels preceding them within the generalized linear model framework. To deal with the high dimensionality, we regularize the regression coefficients through an appropriate choice of priors. The model is fit using a combination of iteratively weighted least squares and expectation-maximization algorithms to estimate the posterior modes and their standard errors. A normal approximation is used for inference. <b><i>Results:</i></b> We conduct simulations to study the proposed method and find that our method has higher power than some standard approaches in several settings for identifying pathways with multiple modest-sized variants. We illustrate the method by analyzing data from two genome-wide association studies on breast and renal cancers. <b><i>Conclusion:</i></b> Our method can be helpful in detecting pathway association.

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