Vis enkel innførsel

dc.contributor.authorSmeland, Olav Bjerkehagenen_US
dc.contributor.authorFrei, Oleksandren_US
dc.contributor.authorShadrin, Alexey A.en_US
dc.contributor.authorO'Connell, Kevinen_US
dc.contributor.authorFan, Chun Chiehen_US
dc.contributor.authorBahrami, Shahramen_US
dc.contributor.authorHolland, Dominicen_US
dc.contributor.authorDjurovic, Srdjanen_US
dc.contributor.authorThompson, Wesley Kurten_US
dc.contributor.authorDale, Andersen_US
dc.contributor.authorAndreassen, Ole Andreasen_US
dc.date.accessioned2019-12-03T12:52:25Z
dc.date.available2019-12-03T12:52:25Z
dc.date.issued2020
dc.PublishedSmeland OB, Frei O, Shadrin AA, O'Connell K, Fan CC, Bahrami S, Holland D, Djurovic S, Thompson WK, Dale A, Andreassen OA. Discovery of shared genomic loci using the conditional false discovery rate approach. Human Genetics. 2019:1-10.eng
dc.identifier.issn1432-1203
dc.identifier.issn0340-6717
dc.identifier.urihttps://hdl.handle.net/1956/21050
dc.description.abstractIn recent years, genome-wide association study (GWAS) sample sizes have become larger, the statistical power has improved and thousands of trait-associated variants have been uncovered, offering new insights into the genetic etiology of complex human traits and disorders. However, a large fraction of the polygenic architecture underlying most complex phenotypes still remains undetected. We here review the conditional false discovery rate (condFDR) method, a model-free strategy for analysis of GWAS summary data, which has improved yield of existing GWAS and provided novel findings of genetic overlap between a wide range of complex human phenotypes, including psychiatric, cardiovascular, and neurological disorders, as well as psychological and cognitive traits. The condFDR method was inspired by Empirical Bayes approaches and leverages auxiliary genetic information to improve statistical power for discovery of single-nucleotide polymorphisms (SNPs). The cross-trait condFDR strategy analyses separate GWAS data, and leverages overlapping SNP associations, i.e., cross-trait enrichment, to increase discovery of trait-associated SNPs. The extension of the condFDR approach to conjunctional FDR (conjFDR) identifies shared genomic loci between two phenotypes. The conjFDR approach allows for detection of shared genomic associations irrespective of the genetic correlation between the phenotypes, often revealing a mixture of antagonistic and agonistic directional effects among the shared loci. This review provides a methodological comparison between condFDR and other relevant cross-trait analytical tools and demonstrates how condFDR analysis may provide novel insights into the genetic relationship between complex phenotypes.en_US
dc.language.isoengeng
dc.publisherSpringer Berlin Heidelbergeng
dc.subjectConditional false discovery rateeng
dc.subjectPleiotropyeng
dc.subjectGenetic overlapeng
dc.subjectPolygenic architectureeng
dc.subjectGenetic correlationeng
dc.titleDiscovery of shared genomic loci using the conditional false discovery rate approachen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2019-09-18T09:30:11Z
dc.description.versionacceptedVersionen_US
dc.rights.holderCopyright 2019 Springer-Verlag GmbH Germany
dc.identifier.doihttps://doi.org/10.1007/s00439-019-02060-2
dc.identifier.cristin1726118
dc.source.journalHuman Genetics
dc.source.pagenumber85–94
dc.identifier.citationHuman Genetics. 2020, 139, 85–94.
dc.source.volume139


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel