Linked Life Data

16240441

Source:http://linkedlifedata.com/resource/pubmed/id/16240441

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-11-23
pubmed:abstractText
Genetically complex diseases are caused by interacting environmental factors and genes. As a consequence, statistical methods that consider multiple unlinked genomic regions simultaneously are desirable. Such consideration, however, may lead to a vast number of different high-dimensional tests whose appropriate analysis pose a problem. Here, we present a method to analyze case-control studies with multiple SNP data without phase information that considers gene-gene interaction effects while correcting appropriately for multiple testing. In particular, we allow for interactions of haplotypes that belong to different unlinked regions, as haplotype analysis often proves to be more powerful than single marker analysis. In addition, we consider different marker combinations at each unlinked region. The multiple testing issue is settled via the minP approach; the P value of the "best" marker/region configuration is corrected via Monte-Carlo simulations. Thus, we do not explicitly test for a specific pre-defined interaction model, but test for the global hypothesis that none of the considered haplotype interactions shows association with the disease. We carry out a simulation study for case-control data that confirms the validity of our approach. When simulating two-locus disease models, our test proves to be more powerful than association methods that analyze each linked region separately. In addition, when one of the tested regions is not involved in the etiology of the disease, only a small amount of power is lost with interaction analysis as compared to analysis without interaction. We successfully applied our method to a real case-control data set with markers from two genes controlling a common pathway. While classical analysis failed to reach significance, we obtained a significant result even after correction for multiple testing with our proposed haplotype interaction analysis. The method described here has been implemented in FAMHAP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0741-0395
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-22
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Haplotype interaction analysis of unlinked regions.
pubmed:affiliation
Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany. becker@imbie.meb.uni-bonn.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't