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dc.contributor.authorAranda-Guillén, Maribel
dc.contributor.authorRøyrvik, Ellen Christine
dc.contributor.authorFletcher-Sandersjöö, Sara
dc.contributor.authorArtaza Alvarez, Haydee Maribel
dc.contributor.authorBotusan, Ileana Ruxandra
dc.contributor.authorGrytaas, Marianne Aardal
dc.contributor.authorHallgren, Åsa
dc.contributor.authorBreivik, Lars Ertesvåg
dc.contributor.authorPettersson, Maria
dc.contributor.authorJørgensen, Anders Palmstrøm
dc.contributor.authorLindstrand, Anna
dc.contributor.authorVogt, Elinor Margrethe
dc.contributor.authorHusebye, Eystein Sverre
dc.contributor.authorKämpe, Olle
dc.contributor.authorWolff, Anette Susanne Bøe
dc.contributor.authorBensing, Sophie
dc.contributor.authorJohansson, Stefan
dc.contributor.authorEriksson, Daniel
dc.date.accessioned2023-06-20T11:56:28Z
dc.date.available2023-06-20T11:56:28Z
dc.date.created2023-06-15T12:58:10Z
dc.date.issued2023
dc.identifier.issn0954-6820
dc.identifier.urihttps://hdl.handle.net/11250/3072292
dc.description.abstractBackground Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients. Methods We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI. Results The genetic susceptibility to AAD—quantified using PRS—was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p < 2e − 16), and 1.2 SD higher in the young patients compared with the old (p = 3e − 4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies. Conclusions The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleA polygenic risk score to help discriminate primary adrenal insufficiency of different etiologiesen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.1111/joim.13649
dc.identifier.cristin2154847
dc.source.journalJournal of Internal Medicineen_US
dc.source.pagenumber96-109en_US
dc.identifier.citationJournal of Internal Medicine. 2023, 294 (1), 96-109.en_US
dc.source.volume294en_US
dc.source.issue1en_US


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