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@ARTICLE{Freytag:120041,
author = {S. Freytag and J. Manitz and M. Schlather and T. Kneib and
C. I. Amos and A. Risch$^*$ and J. Chang$^*$ and J. Heinrich
and H. Bickeböller},
title = {{A} network-based kernel machine test for the
identification of risk pathways in genome-wide association
studies.},
journal = {Human heredity},
volume = {76},
number = {2},
issn = {1423-0062},
address = {Basel},
publisher = {Karger},
reportid = {DKFZ-2017-00628},
pages = {64 - 75},
year = {2013},
abstract = {Biological pathways provide rich information and biological
context on the genetic causes of complex diseases. The
logistic kernel machine test integrates prior knowledge on
pathways in order to analyze data from genome-wide
association studies (GWAS). In this study, the kernel
converts the genomic information of 2 individuals into a
quantitative value reflecting their genetic similarity. With
the selection of the kernel, one implicitly chooses a
genetic effect model. Like many other pathway methods, none
of the available kernels accounts for the topological
structure of the pathway or gene-gene interaction types.
However, evidence indicates that connectivity and
neighborhood of genes are crucial in the context of GWAS,
because genes associated with a disease often interact.
Thus, we propose a novel kernel that incorporates the
topology of pathways and information on interactions. Using
simulation studies, we demonstrate that the proposed method
maintains the type I error correctly and can be more
effective in the identification of pathways associated with
a disease than non-network-based methods. We apply our
approach to genome-wide association case-control data on
lung cancer and rheumatoid arthritis. We identify some
promising new pathways associated with these diseases, which
may improve our current understanding of the genetic
mechanisms.},
cin = {C010 / C020},
ddc = {570},
cid = {I:(DE-He78)C010-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24434848},
pmc = {pmc:PMC4026009},
doi = {10.1159/000357567},
url = {https://inrepo02.dkfz.de/record/120041},
}