Pathway-based genetic analysis of preterm birth.
Alper Uzun1, Andrew T Dewan, Sorin Istrail
1Women and Infants Hospital of Rhode Island, Department of Pediatrics, and Brown Alpert Medical School, Providence, RI 02905, USA.
Genomics
|January 10, 2013
Summary
This study refined gene analysis for preterm birth (PTB), a major US health issue. Using a custom gene database improved genome-wide association study (GWAS) power, revealing significant gene interactions for PTB.
Area of Science:
- Genetics
- Reproductive Health
- Bioinformatics
Background:
- Preterm birth (PTB) affects 12% of US births, with complex genetic underpinnings.
- Existing genome-wide association studies (GWAS) have had limited success in identifying PTB-associated genes.
- A curated database of PTB-related genes can enhance genetic analyses.
Purpose of the Study:
- To identify significant gene-gene interactions associated with preterm birth.
- To evaluate the efficacy of a curated gene set compared to a genome-wide approach in GWAS.
- To enhance statistical power and discovery in PTB genetic research.
Main Methods:
- Developed a custom database for preterm birth (dbPTB) with curated genes.
- Analyzed GWAS data from nearly 2000 mothers (preterm and term).
- Performed pathway-based analysis using both curated genes and a genome-wide approach, applying FDR correction.
Main Results:
- Identified 19 significant pathways associated with preterm birth after FDR correction.
- Pathway analysis using curated genes showed greater significance than the genome-wide approach in 15 out of 19 pathways.
- Demonstrated enhanced statistical power and discovery by integrating a validated gene set into GWAS.
Conclusions:
- A curated gene set approach significantly enhances GWAS for identifying preterm birth-related gene interactions.
- This method offers a powerful strategy for analyzing complex genetic diseases, even with previously unsuccessful GWAS data.
- dbPTB provides a valuable resource for advancing preterm birth research and understanding its genetic etiology.
