Abstract
For genome-wide association studies, it has been increasingly recognized that the popular locus-by-locus search for DNA variants associated with disease susceptibility may not be effective, especially when there are interactions between or among multiple loci, for which a multi-loci search strategy may be more productive. However, even if computationally feasible, a genome-wide search over all possible multiple loci requires exploring a huge model space and making costly adjustment for multiple testing, leading to reduced statistical power. On the other hand, there are accumulating data suggesting that protein products of many disease-causing genes tend to interact with each other, or cluster in the same biological pathway. To incorporate this prior knowledge and existing data on gene networks, we propose a gene network-based method to improve statistical power over that of the exhaustive search by giving higher weights to models involving genes nearby in a network. We use simulated data under realistic scenarios, including a large-scale human protein-protein interaction network and 23 known ataxia-causing genes, to demonstrate potential gain by our proposed method when disease-genes are clustered in a network.
References
Jan 14, 2003·Nature Genetics·Kirk E LohmuellerJoel N Hirschhorn
Oct 4, 2003·Genome Research·Suraj PeriAkhilesh Pandey
Jan 22, 2004·Nature Reviews. Genetics·Albert-László Barabási, Zoltán N Oltvai
May 29, 2004·Nature Genetics·Andrew G Fraser, Edward M Marcotte
Dec 21, 2004·Nucleic Acids Research·C AlfaranoC W V Hogue
Dec 21, 2004·Nucleic Acids Research·G Joshi-TopeL Stein
Jan 8, 2005·Genetic Epidemiology·Kathryn RoederB Devlin
Mar 29, 2005·Nature Genetics·Jonathan MarchiniLon R Cardon
May 17, 2005·Genome Biology·Arun K RamaniEdward M Marcotte
Jun 7, 2005·Biochimie·Gaëtane MacéFilippo Rosselli
Jun 9, 2005·Traffic·Santiago M Di Pietro, Esteban C Dell'Angelica
Sep 20, 2005·Cell·Ulrich StelzlErich E Wanker
Sep 29, 2005·Nature·Jean-François RualMarc Vidal
Feb 28, 2006·Nature Genetics·T K B GandhiAkhilesh Pandey
Apr 14, 2006·Journal of Medical Genetics·M OtiH G Brunner
May 23, 2006·Cell·Janghoo LimHuda Y Zoghbi
Feb 3, 2007·Genetic Epidemiology·Valentin DinuHongyu Zhao
Apr 17, 2007·Science·Timothy M FraylingMark I McCarthy
Jun 6, 2007·Genetic Epidemiology·Kathryn RoederLarry Wasserman
Aug 19, 2007·Genome Research·Jimmy LinVictor E Velculescu
Aug 19, 2007·American Journal of Human Genetics·Iuliana Ionita-LazaChristoph Lange
Oct 13, 2007·Science·Laura D WoodBert Vogelstein
Oct 18, 2007·Molecular Systems Biology·Han-Yu ChuangTrey Ideker
Oct 30, 2007·American Journal of Human Genetics·Kai WangMaja Bucan
Dec 20, 2007·Molecular Systems Biology·Qinghua CuiEdwin Wang
Apr 3, 2008·Genome Research·Trey Ideker, Roded Sharan
Citations
Nov 20, 2009·Journal of Neurology·Pia Irene Anna RossiAldamaria Puliti
Jul 28, 2012·Nature Genetics·Andrea CalifanoEric Schadt
Jan 8, 2010·Bioinformatics·Jason H MooreScott M Williams
Feb 27, 2010·Bioinformatics·Saket Navlakha, Carl Kingsford
Sep 5, 2009·Genome Biology·Bolan LinghuCharles Delisi
Dec 10, 2013·Current Genetic Medicine Reports·Yu Liu, Mark R Chance
Feb 18, 2016·Human Genetics·Anne ZuffereyPierre Fontana
Dec 17, 2008·Medical Hypotheses·Kristen F Gorman, Felix Breden
Jan 17, 2012·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Celine LefebvreAndrea Califano
Apr 13, 2011·Genetic Epidemiology·Tune H PersSøren Brunak
Nov 13, 2014·Psychophysiology·William G IaconoStephen M Malone
May 14, 2011·Genomics·Lily WangZhongming Zhao
Nov 20, 2014·PloS One·Catarina CorreiaAstrid M Vicente
Jan 18, 2014·Human Heredity·Saskia FreytagHeike Bickeböller
Nov 19, 2010·Nature Reviews. Genetics·Kai WangHakon Hakonarson
Aug 3, 2016·Medical Sciences : Open Access Journal·Alireza TorabiChun Xu
May 13, 2017·Scientific Reports·Luis E LeónGabriela M Repetto
Aug 9, 2017·Computational and Mathematical Methods in Medicine·Stefanie FriedrichsBenjamin Hofner