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Genomics. 2013 Mar;101(3):163-70. doi: 10.1016/j.ygeno.2012.12.005. Epub 2013 Jan 6.

Pathway-based genetic analysis of preterm birth.

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  • 1Women and Infants Hospital of Rhode Island, Department of Pediatrics, and Brown Alpert Medical School, Providence, RI 02905, USA.

Abstract

Preterm birth in the United States is now 12%. Multiple genes, gene networks, and variants have been associated with this disease. Using a custom database for preterm birth (dbPTB) with a refined set of genes extensively curated from literature and biological databases, we analyzed GWAS of preterm birth for complete genotype data on nearly 2000 preterm and term mothers. We used both the curated genes and a genome-wide approach to carry out a pathway-based analysis. There were 19 significant pathways, which withstood FDR correction for multiple testing that were identified using both the curated genes and the genome-wide approach. The analysis based on the curated genes was more significant than genome-wide in 15 out of 19 pathways. This approach demonstrates the use of a validated set of genes, in the analysis of otherwise unsuccessful GWAS data, to identify gene-gene interactions in a way that enhances statistical power and discovery.

Copyright © 2013 Elsevier Inc. All rights reserved.

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