Pathway-Based Genetic Analysis of Preterm Birth.

Brown Alpert Medical School, Providence, RI
Genomics (Impact Factor: 2.28). 01/2013; 101(3). DOI: 10.1016/j.ygeno.2012.12.005
Source: PubMed


Preterm birth in the United States is now 12%. Multiple genes, gene networks, 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 a 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.

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    • "However, in this dataset, gene variants with genome-wide statistical significance have not been found. Recent pathway-based, rather than gene-based, analyses using a custom database of genes curated from existing literature for preterm birth (dbPTB), have implicated several potentially relevant pathways that can be used to elucidate further gene-gene and gene-environment interactions [52,57]. Further meta-analysis with emerging new data from other groups should provide additional power for the detection of associations. "
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