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dc.contributor.authorLancour, Danielen_US
dc.contributor.authorNaj, Adamen_US
dc.contributor.authorMayeux, Richarden_US
dc.contributor.authorHaines, Jonathan L.en_US
dc.contributor.authorPericak-Vance, Margaret A.en_US
dc.contributor.authorSchellenberg, Gerard C.en_US
dc.contributor.authorCrovella, Marken_US
dc.contributor.authorFarrer, Lindsay A.en_US
dc.contributor.authorKasif, Simonen_US
dc.date.accessioned2019-03-21T17:18:30Z
dc.date.available2019-03-21T17:18:30Z
dc.date.issued2018-04-01
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000431115700019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654
dc.identifier.citationDaniel Lancour, Adam Naj, Richard Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Gerard C Schellenberg, Mark Crovella, Lindsay A Farrer, Simon Kasif. 2018. "One for all and all for One: Improving replication of genetic studies through network diffusion." PLOS GENETICS, Volume 14, Issue 4, pp. ? - ? (20). https://doi.org/10.1371/journal.pgen.1007306
dc.identifier.issn1553-7404
dc.identifier.urihttps://hdl.handle.net/2144/34348
dc.description.abstractImproving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS) approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD) GWAS dataset. Using a statistical bootstrap approach, we cross-validated the method and for the first time showed that a network approach improves the expected replication rates in GWAS studies. Several novel AD genes were predicted including CR2, SHARPIN, and PTPN2. Our re-prioritized results are enriched for established known AD-associated biological pathways including inflammation, immune response, and metabolism, whereas standard non-prioritized results were not. Our findings support a strategy of considering network information when investigating genetic risk factors.en_US
dc.description.sponsorshipThe National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible; Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689-01); NACC, U01 AG016976; NIA LOAD (Columbia University), U24 AG026395, R01AG041797; Banner Sun Health Research Institute P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CM 29769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG048927, RO1AG33193; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, U01 AG006781, U01 HG004610, U01 HG006375; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819 R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653, AG041718, AG07562, AG02365; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, 1101 AG027944,AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; University of Wisconsin, P50 AG033514; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant # NS39764, NIMH MH60451 and by Glaxo Smith Kline. Support was also from the Alzheimer's Association (LAF, IIRG-08-89720; MP-V, IIRG-05-14147), the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program, and BrightFocus Foundation (MP-V, A2111048). P.S.G.-H. is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232 to AJM and MJH. The Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr.Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer's Research UK (ARUK), BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland BreinbrekendWerk, International Parkinson Fonds, InternationaleStiching Alzheimer Onderzoek), Institut de Neuropatologia, ServeiAnatomiaPatologica, Universitat de Barcelona. ADNI data collection and sharing was funded by the National Institutes of Health Grant U01 AG024904 and Department of Defense award number W81XWH-12-2-0012. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; Eurolmmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (U01 AG032984 - National Institutes of Health, National Institute on Aging (NIH-NIA); RC2 AG036528 - National Institutes of Health, National Institute on Aging (NIH-NIA); U24 AG21886 - National Institute on Aging (NIA); NS39764 - NINDS; MH60451 - NIMH; Glaxo Smith Kline; IIRG-08-89720 - Alzheimer's Association; IIRG-05-14147 - Alzheimer's Association; US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program; A2111048 - BrightFocus Foundation; Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of Health Research; Kronos Science; AG041232 - NIA; Banner Alzheimer's Foundation; Johnnie B. Byrd Sr. Alzheimer's Institute; Medical Research Council; state of Arizona; NHS trusts; Newcastle University; Higher Education Funding Council for England (HEFCE); Alzheimer's Research UK (ARUK); BRACE; North Bristol NHS Trust Research and Innovation Department; DeNDRoN; Stichting MS Research; Brain Net Europe; Hersenstichting Nederland BreinbrekendWerk; International Parkinson Fonds; InternationaleStiching Alzheimer Onderzoek; U01 AG024904 - National Institutes of Health; W81XWH-12-2-0012 - Department of Defense; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; Eurolmmun; F. Hoffmann-La Roche Ltd; Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; Transition Therapeutics; Canadian Institutes of Health Research)en_US
dc.format.extent20 p.en_US
dc.languageEnglish
dc.language.isoen_US
dc.publisherPUBLIC LIBRARY SCIENCEen_US
dc.relation.ispartofPLOS GENETICS
dc.rightsAttribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectGenetics & heredityen_US
dc.subjectFamilial Alzheimer's diseaseen_US
dc.subjectGenome wide associationen_US
dc.subjectGenotype imputationen_US
dc.subjectAfrican-Americansen_US
dc.subjectVariantsen_US
dc.subjectOnseten_US
dc.subjectLocien_US
dc.subjectMeta-analysisen_US
dc.subjectMutationsen_US
dc.subjectSusceptibilityen_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectDatasets as topicsen_US
dc.subjectGenome-wide association studyen_US
dc.subjectHumansen_US
dc.subjectProtein interaction mapsen_US
dc.subjectReproducibility of resultsen_US
dc.subjectRisk factorsen_US
dc.subjectSupport vector machineen_US
dc.subjectGeneticsen_US
dc.subjectDevelopmental biologyen_US
dc.titleOne for all and all for one: improving replication of genetic studies through network diffusionen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1371/journal.pgen.1007306
pubs.elements-sourceweb-of-scienceen_US
pubs.notesEmbargo: No embargoen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Computer Scienceen_US
pubs.organisational-groupBoston University, College of Engineeringen_US
pubs.organisational-groupBoston University, College of Engineering, Department of Biomedical Engineeringen_US
pubs.organisational-groupBoston University, School of Medicineen_US
pubs.publication-statusPublisheden_US
dc.identifier.orcid0000-0002-5005-7019 (Crovella, Mark)


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