What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations
| dc.contributor.author | Panagiotou, O. A. | en |
| dc.contributor.author | Ioannidis, J. P. | en |
| dc.date.accessioned | 2015-11-24T19:16:04Z | |
| dc.date.available | 2015-11-24T19:16:04Z | |
| dc.identifier.issn | 1464-3685 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/21609 | |
| dc.rights | Default Licence | - |
| dc.title | What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations | en |
| heal.abstract | BACKGROUND: Robust replication is a sine qua non for the rigorous documentation of proposed associations in the genome-wide association (GWA) setting. Currently, associations of common variants reaching P </= 5 x 10(-8) are considered replicated. However, there is some ambiguity about the most suitable threshold for claiming genome-wide significance. METHODS: We defined as 'borderline' associations those with P > 5 x 10(-8) and P </=1 x 10(-7). The eligible associations were retrieved using the 'Catalog of Published Genome-Wide Association Studies'. For each association we assessed whether it reached P </= 5 x 10(-8) with inclusion of additional data from subsequent GWA studies. RESULTS: Thirty-four eligible genotype-phenotype associations were evaluated with data and clarifications contributed from diverse investigators. Replication data from subsequent GWA studies could be obtained for 26 of them. Of those, 19 associations (73%) reached P </= 5 x 10(-8) for the same or a related trait implicating either the exact same allele or one in very high linkage disequilibrium and 17 reached P < 10(-8). If the seven associations that did not reach P </= 5 x 10(-8) when additional data were considered are assumed to have been false-positives, the false-discovery rate for borderline associations is estimated to be 27% [95% confidence interval (CI) 12-48%]. For five associations, the current P-value is > 10(-6) [corresponding false-discovery rate 19% (95% CI 7-39%)]. CONCLUSION: A substantial proportion, but not all, of the associations with borderline genome-wide significance represent replicable, possibly genuine associations. Our empirical evaluation suggests a possible relaxation in the current GWS threshold. | en |
| heal.access | campus | - |
| heal.fullTextAvailability | TRUE | - |
| heal.identifier.primary | 10.1093/ije/dyr178 | - |
| heal.identifier.secondary | http://www.ncbi.nlm.nih.gov/pubmed/22253303 | - |
| heal.identifier.secondary | http://ije.oxfordjournals.org/content/41/1/273.full.pdf | - |
| heal.journalName | Int J Epidemiol | en |
| heal.journalType | peer-reviewed | - |
| heal.language | en | - |
| heal.publicationDate | 2012 | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής | el |
| heal.type | journalArticle | - |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.type.en | Journal article | en |
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