Meta-analysis in genome-wide association datasets: strategies and application in Parkinson disease

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dc.contributor.authorEvangelou, E.en
dc.contributor.authorMaraganore, D. M.en
dc.contributor.authorIoannidis, J. P.en
dc.date.accessioned2015-11-24T19:04:46Z
dc.date.available2015-11-24T19:04:46Z
dc.identifier.issn1932-6203-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/20101
dc.rightsDefault Licence-
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenome-Wide Association Study/*statistics & numerical dataen
dc.subjectGenotypeen
dc.subjectHumansen
dc.subjectMeta-Analysis as Topicen
dc.subjectOdds Ratioen
dc.subjectParkinson Disease/*epidemiology/geneticsen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectProspective Studiesen
dc.subjectSiblingsen
dc.titleMeta-analysis in genome-wide association datasets: strategies and application in Parkinson diseaseen
heal.abstractBACKGROUND: Genome-wide association studies hold substantial promise for identifying common genetic variants that regulate susceptibility to complex diseases. However, for the detection of small genetic effects, single studies may be underpowered. Power may be improved by combining genome-wide datasets with meta-analytic techniques. METHODOLOGY/PRINCIPAL FINDINGS: Both single and two-stage genome-wide data may be combined and there are several possible strategies. In the two-stage framework, we considered the options of (1) enhancement of replication data and (2) enhancement of first-stage data, and then, we also considered (3) joint meta-analyses including all first-stage and second-stage data. These strategies were examined empirically using data from two genome-wide association studies (three datasets) on Parkinson disease. In the three strategies, we derived 12, 5, and 49 single nucleotide polymorphisms that show significant associations at conventional levels of statistical significance. None of these remained significant after conservative adjustment for the number of performed analyses in each strategy. However, some may warrant further consideration: 6 SNPs were identified with at least 2 of the 3 strategies and 3 SNPs [rs1000291 on chromosome 3, rs2241743 on chromosome 4 and rs3018626 on chromosome 11] were identified with all 3 strategies and had no or minimal between-dataset heterogeneity (I(2) = 0, 0 and 15%, respectively). Analyses were primarily limited by the suboptimal overlap of tested polymorphisms across different datasets (e.g., only 31,192 shared polymorphisms between the two tier 1 datasets). CONCLUSIONS/SIGNIFICANCE: Meta-analysis may be used to improve the power and examine the between-dataset heterogeneity of genome-wide association studies. Prospective designs may be most efficient, if they try to maximize the overlap of genotyping platforms and anticipate the combination of data across many genome-wide association studies.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1371/journal.pone.0000196-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/17332845-
heal.identifier.secondaryhttp://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0000196&representation=PDF-
heal.journalNamePLoS Oneen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2007-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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