A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples

BMC Genetics
Paola SebastianiClinton T Baldwin

Abstract

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. 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. 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...Continue Reading

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Jun 13, 2009·European Journal of Applied Physiology·Ildus I AhmetovViktor A Rogozkin
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Methods Mentioned

BETA
genotyping
chromosomal aberrations
chip

Software Mentioned

GSEA
Illumina
dbSNP
PLINK
R
EASE
UCSC browser
Illumina loss of heterozygosity ( LOH ) and Copy Number analys...
SNPPer

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