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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/31188

Title: A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples
Authors: Sebastiani, Paola
Zhao, Zhenming
Abad-Grau, María M.
Riva, Alberto
Hartley, Stephen W.
Sedgewick, Amanda E.
Doria, Alessandro
Montano, Monty
Melista, Efthymia
Terry, Dellara
Perls, Thomas T.
Steinberg, Martin H.
Baldwin, Clinton T.
Issue Date: 2008
Abstract: [Background] One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. [Results] We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. [Conclusion] Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects.
Sponsorship: Supported by NHLBI grants R21 HL080463 (PS); R01 HL68970 (MHS); K-24, AG025727 (TP); K23 AG026754 (D.T.).
Publisher: Biomed Central
Keywords: Bayes theorem
Computational biology
DNA
Fetal hemoglobin
Gene frequency
Genetic markers
Genome
Genotype
Linkage disequilibrium
Sensitivity and specificity
URI: http://hdl.handle.net/10481/31188
ISSN: 1471-2156
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Sabastiani, P.; et al. A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples. BMC Genetics, 9: 6 (2008). [http://hdl.handle.net/10481/31188]
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