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Abstract Details
Activity Number:
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277
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Type:
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Topic Contributed
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Date/Time:
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Tuesday, July 31, 2012 : 8:30 AM to 10:20 AM
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Sponsor:
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Biometrics Section
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Abstract - #305099 |
Title:
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An Integrative Genomics Approach for Identifying Methylation-Mediated eQTLs
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Author(s):
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Karen Conneely*+
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Companies:
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Address:
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615 Michael Street, Atlanta, GA, 30322, United States
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Keywords:
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genetics ;
methylation ;
eQTL ;
epigenetics ;
expression
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Abstract:
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With the increasing availability of multiple types of genomic data within studies, it has become possible to investigate the relationship between sequence variation, DNA methylation, and expression of specific genes. However, the density of SNPs and CpG sites available on contemporary genome-wide arrays is both a blessing and a curse, since even within a single gene there may be hundreds or thousands of SNP-CpG combinations. We present a method to reduce the dimensionality of these comparisons in order to elucidate the role of DNA methylation as a potential mediator underlying eQTLs (expression quantitative trait loci). For each expressed gene transcript, we define sets of proximal SNPs and CpG sites. To identify eQTLs, we model transcript expression levels as a nonparametric function of the SNP genotypes and a linear function of other covariates. We follow up potential eQTLs by fitting a similar semiparametric regression based on both the SNP set and the set of CpG sites. We next extend standard tests for mediation to this semi-parametric framework to identify eQTLs under mediation by DNA methylation. We illustrate and test our method with both simulated and real data.
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