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dc.contributor.authorNorheim, Katrine Brække
dc.contributor.authorImgenberg-Kreuz, Juliana
dc.contributor.authorAlexsson, Andrei
dc.contributor.authorJohnsen, Svein Joar Auglæn
dc.contributor.authorBårdsen, Kjetil
dc.contributor.authorBrun, Johan Gorgas
dc.contributor.authorDehkordi, Rezvan Kiani
dc.contributor.authorTheander, Elke
dc.contributor.authorMandl, Thomas
dc.contributor.authorJonsson, Roland
dc.contributor.authorNg, Wan-Fai
dc.contributor.authorLessard, Christopher J
dc.contributor.authorRasmussen, Astrid
dc.contributor.authorSivilis, Kathy
dc.contributor.authorRönnblom, Lars
dc.contributor.authorOmdal, Roald
dc.date.accessioned2022-04-19T12:58:41Z
dc.date.available2022-04-19T12:58:41Z
dc.date.created2022-02-04T14:28:08Z
dc.date.issued2021
dc.identifier.issn2056-5933
dc.identifier.urihttps://hdl.handle.net/11250/2991351
dc.description.abstractObjectives Fatigue is common and severe in primary Sjögren’s syndrome (pSS). The aim of this study was to identify genetic determinants of fatigue in pSS through a genome-wide association study. Methods Patients with pSS from Norway, Sweden, UK and USA with fatigue and genotype data available were included. After genotype imputation and quality control, 682 patients and 4 966 157 genetic markers were available. Association analysis in each cohort using linear regression with fatigue as a continuous variable and meta-analyses between the cohorts were performed. Results Meta-analysis of the Norwegian and Swedish cohorts identified five polymorphisms within the same linkage disequilibrium block at the receptor transporter protein 4 (RTP4)/MASP1 locus associated with fatigue with genome-wide significance (GWS) (p<5×10−8). Patients homozygous for the major allele scored 25 mm higher on the fatigue Visual Analogue Scale than patients homozygous for the minor allele. There were no variants associated with fatigue with GWS in meta-analyses of the US/UK cohorts, or all four cohorts. RTP4 expression in pSS B cells was upregulated and positively correlated with the type I interferon score. Expression quantitative trait loci effects in whole blood for fatigue-associated variants at RTP4/MASP1 and levels of RTP4 and MASP1 expression were identified. Conclusion Genetic variations at RTP4/MASP1 are associated with fatigue in Scandinavian pSS patients. RTP4 encodes a Golgi chaperone that influences opioid pain receptor function and MASP1 is involved in complement activation. These results add evidence for genetic influence over fatigue in pSS.en_US
dc.language.isoengen_US
dc.publisherBMJen_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/deed.no*
dc.titleGenetic variants at the RTP4/MASP1 locus are associated with fatigue in Scandinavian patients with primary Sjögren’s syndromeen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.source.articlenumbere001832en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.1136/rmdopen-2021-001832
dc.identifier.cristin1997901
dc.source.journalRMD Openen_US
dc.identifier.citationRMD Open. 2021, 7, e001832.en_US
dc.source.volume7en_US


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Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal