Dataset Information

Identification of therapeutic targets from genetic association studies using hierarchical component analysis.

ABSTRACT:

Background

Mapping disease-associated genetic variants to complex disease pathophysiology is a major challenge in translating findings from genome-wide association studies into novel therapeutic opportunities. The difficulty lies in our limited understanding of how phenotypic traits arise from non-coding genetic variants in highly organized biological systems with heterogeneous gene expression across cells and tissues.

Results

We present a novel strategy, called GWAS component analysis, for transferring disease associations from single-nucleotide polymorphisms to co-expression modules by stacking models trained using reference genome and tissue-specific gene expression data. Application of this method to genome-wide association studies of blood cell counts confirmed that it could detect gene sets enriched in expected cell types. In addition, coupling of our method with Bayesian networks enables GWAS components to be used to discover drug targets.

Conclusions

We tested genome-wide associations of four disease phenotypes, including age-related macular degeneration, Crohn's disease, ulcerative colitis and rheumatoid arthritis, and demonstrated the proposed method could select more functional genes than S-PrediXcan, the previous single-step model for predicting gene-level associations from SNP-level associations.

SUBMITTER: Lee HC

PROVIDER: S-EPMC7301559 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Identification of therapeutic targets from genetic association studies using hierarchical component analysis.

Lee Hao-Chih HC Ichikawa Osamu O Glicksberg Benjamin S BS Divaraniya Aparna A AA Becker Christine E CE Agarwal Pankaj P Dudley Joel T JT

BioData mining 20200617

<h4>Background</h4>Mapping disease-associated genetic variants to complex disease pathophysiology is a major challenge in translating findings from genome-wide association studies into novel therapeutic opportunities. The difficulty lies in our limited understanding of how phenotypic traits arise from non-coding genetic variants in highly organized biological systems with heterogeneous gene expression across cells and tissues.<h4>Results</h4>We present a novel strategy, called GWAS component ana ...[more]

PMID: 32565911

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Dataset Information

Identification of therapeutic targets from genetic association studies using hierarchical component analysis.

Background

Results

Conclusions

Publications

Identification of therapeutic targets from genetic association studies using hierarchical component analysis.

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