X-chromosome variants are associated with aldosterone producing adenomas
dc.contributor.author | Dutta, Ravi Kumar | |
dc.contributor.author | Larsson, Malin | |
dc.contributor.author | Arnesen, Thomas | |
dc.contributor.author | Heie, Anette | |
dc.contributor.author | Walz, Martin K. | |
dc.contributor.author | Alesina, Piero | |
dc.contributor.author | Gimm, Oliver | |
dc.contributor.author | Söderkvist, Peter | |
dc.date.accessioned | 2022-04-11T11:58:32Z | |
dc.date.available | 2022-04-11T11:58:32Z | |
dc.date.created | 2021-07-09T14:27:01Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://hdl.handle.net/11250/2990937 | |
dc.description.abstract | Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To date, no studies have used a genome-wide association study (GWAS) approach to search for predisposing loci for APAs. Thus, we investigated Scandinavian APA cases (n = 35) and Swedish controls (n = 60) in a GWAS and discovered a susceptibility locus on chromosome Xq13.3 (rs2224095, OR = 7.9, 95% CI = 2.8–22.4, P = 1 × 10–7) in a 4-Mb region that was significantly associated with APA. Direct genotyping of sentinel SNP rs2224095 in a replication cohort of APAs (n = 83) and a control group (n = 740) revealed persistently strong significance (OR = 6.1, 95% CI = 3.5–10.6, p < 0.0005). We sequenced an adjacent gene, MAGEE1, of the sentinel SNP and identified a rare variant in one APA, p.Gly327Glu, which is complementary to other mutations in our primary cohort. Expression quantitative trait loci (eQTL) were investigated on the X-chromosome, and 24 trans-eQTL were identified. Some of the genes identified by trans-eQTL point towards a novel mechanistic explanation for the association of the SNPs with APAs. In conclusion, our study provides further insights into the genetic basis of APAs. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Nature | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | X-chromosome variants are associated with aldosterone producing adenomas | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2021 The Author(s) | en_US |
dc.source.articlenumber | 10562 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1038/s41598-021-89986-8 | |
dc.identifier.cristin | 1921202 | |
dc.source.journal | Scientific Reports | en_US |
dc.identifier.citation | Scientific Reports. 2021, 11 (1), 10562. | en_US |
dc.source.volume | 11 | en_US |
dc.source.issue | 1 | en_US |
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