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Activity Number:
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473
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Type:
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Contributed
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Date/Time:
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Wednesday, August 5, 2009 : 10:30 AM to 12:20 PM
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Sponsor:
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Biometrics Section
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| Abstract - #305235 |
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Title:
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A Unified Procedure for Evaluating HWE and Association in Genome-Wide Association Studies That Reduces False Positives
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Author(s):
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Stefan Boehringer*+ and Hajo Holzmann and Johannes Hebebrand
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Companies:
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Institut für Humangenetik and Universität Marburg and University of Duisburg-Essen
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Address:
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Hufelandstr. 55, Universitätsklinikum Essen, Essen, 45122, Germany
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Keywords:
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Hardy-Weinberg Equilibrium ; Genome-Wide Association ; Case Control ; False discovery Rate ; SNP ; Association Testing
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Abstract:
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In current genome wide association studies (GWAs) based on a case-control design, single nucleotide polymorphisms (SNPs) are typically evaluated for an association test and a Hardy-Weinberg equilibrium (HWE) goodness-of-fit test. SNPs are then excluded from analysis based on a HWE cutoff to avoid false positives. We have established a conditional genotype based test that conditions the Pearson Chi-Square test in the 3x2 contingency table on the HWE statistic in the control group. We develop the asymptotic theory and derive the asymptotic distribution. We show by simulations, that our test is more powerful than the unconditional Pearson test under HWE in the control group. Moreover, an important additional advantage is a better ranking of SNPs in GWAs as HWE is accounted for in computing p-values of SNP association. We demonstrate this effect on a data set in an obesity study.
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