BAYESIAN MODEL SEARCH AND MULTILEVEL INFERENCE FOR SNP ASSOCIATION STUDIES.

dc.contributor.author

Wilson, MA

dc.contributor.author

Iversen, ES

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Clyde, MA

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Schmidler, SC

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Schildkraut, JM

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United States

dc.date.accessioned

2014-03-24T16:43:11Z

dc.date.issued

2010-09-01

dc.description.abstract

Technological advances in genotyping have given rise to hypothesis-based association studies of increasing scope. As a result, the scientific hypotheses addressed by these studies have become more complex and more difficult to address using existing analytic methodologies. Obstacles to analysis include inference in the face of multiple comparisons, complications arising from correlations among the SNPs (single nucleotide polymorphisms), choice of their genetic parametrization and missing data. In this paper we present an efficient Bayesian model search strategy that searches over the space of genetic markers and their genetic parametrization. The resulting method for Multilevel Inference of SNP Associations, MISA, allows computation of multilevel posterior probabilities and Bayes factors at the global, gene and SNP level, with the prior distribution on SNP inclusion in the model providing an intrinsic multiplicity correction. We use simulated data sets to characterize MISA's statistical power, and show that MISA has higher power to detect association than standard procedures. Using data from the North Carolina Ovarian Cancer Study (NCOCS), MISA identifies variants that were not identified by standard methods and have been externally "validated" in independent studies. We examine sensitivity of the NCOCS results to prior choice and method for imputing missing data. MISA is available in an R package on CRAN.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/21179394

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1932-6157

dc.identifier.uri

https://hdl.handle.net/10161/8405

dc.language

eng

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Institute of Mathematical Statistics

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Ann Appl Stat

dc.title

BAYESIAN MODEL SEARCH AND MULTILEVEL INFERENCE FOR SNP ASSOCIATION STUDIES.

dc.type

Journal article

duke.contributor.orcid

Clyde, MA|0000-0002-3595-1872

duke.contributor.orcid

Schmidler, SC|0009-0006-3733-3716

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/21179394

pubs.begin-page

1342

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1364

pubs.issue

3

pubs.organisational-group

Clinical Science Departments

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Community and Family Medicine

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Community and Family Medicine, Prevention Research

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Computer Science

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Duke

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Duke Cancer Institute

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Institutes and Centers

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School of Medicine

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Statistical Science

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Trinity College of Arts & Sciences

pubs.publication-status

Published

pubs.volume

4

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