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Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

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dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor.author DBDS Genetic Consortium
dc.contributor.author GO Consortium
dc.date.accessioned 2022-04-07T01:02:09Z
dc.date.available 2022-04-07T01:02:09Z
dc.date.issued 2022-02
dc.identifier.citation DBDS Genetic Consortium & GO Consortium 2022 , ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ' , Nature Communications , vol. 13 , no. 1 , 634 . https://doi.org/10.1038/s41467-022-28167-1
dc.identifier.issn 2041-1723
dc.identifier.other PURE: 46886972
dc.identifier.other PURE UUID: 14dbc3e4-2d57-4eec-9a66-7e27a48be659
dc.identifier.other Scopus: 85123973763
dc.identifier.uri https://hdl.handle.net/20.500.11815/3028
dc.description Funding Information: We thank all participants in the various studies included here, for their valuable contribution to research. We thank all investigators and colleagues in Iceland who contributed to data collection, phenotypic characterization of clinical samples, genotyping and analysis of the whole-genome association data. We acknowledge participants and investigators of the FinnGen study in Finland, the DBDS-CHB studies in Denmark, and the UK Biobank in Great Britain. This research has been conducted using the UK Biobank Resource under Application Number 24898. The financial support from the European Commission to the painFACT project (H2020-2020-848099, T.E.T.) is acknowledged. K.B., T.F.H., and S.B. acknowledge the Novo Nordisk Foundation (grants NNF17OC0027594 K.B., T.F.H., S.B., and NNF14CC0001 K.B., T.F.H., S.B.). Funding Information: We thank all participants in the various studies included here, for their valuable contribution to research. We thank all investigators and colleagues in Iceland who contributed to data collection, phenotypic characterization of clinical samples, genotyping and analysis of the whole-genome association data. We acknowledge participants and investigators of the FinnGen study in Finland, the DBDS-CHB studies in Denmark, and the UK Biobank in Great Britain. This research has been conducted using the UK Biobank Resource under Application Number 24898. The financial support from the European Commission to the painFACT project (H2020-2020-848099, T.E.T.) is acknowledged. K.B., T.F.H., and S.B. acknowledge the Novo Nordisk Foundation (grants NNF17OC0027594 K.B., T.F.H., S.B., and NNF14CC0001 K.B., T.F.H., S.B.). Publisher Copyright: © 2022, The Author(s).
dc.description.abstract Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.
dc.format.extent
dc.language.iso en
dc.relation.ispartofseries Nature Communications; 13(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Heila- og taugaskurðlæknisfræði
dc.subject Gigtarlæknisfræði
dc.subject Náttúrufræðingar
dc.subject Intervertebral Disc Degeneration
dc.subject Intervertebral Disc Displacement
dc.subject Back Pain
dc.subject Genome-Wide Association Study
dc.subject Chemistry (all)
dc.subject Biochemistry, Genetics and Molecular Biology (all)
dc.subject Physics and Astronomy (all)
dc.title Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 35110524
dc.identifier.doi https://doi.org/10.1038/s41467-022-28167-1
dc.relation.url http://www.scopus.com/inward/record.url?scp=85123973763&partnerID=8YFLogxK
dc.contributor.department Office of Division of Diagnostic and Support Services
dc.contributor.department Faculty of Medicine
dc.contributor.department Faculty of Industrial Engineering, Mechanical Engineering and Computer Science
dc.contributor.department Faculty of Pharmaceutical Sciences
dc.contributor.department Internal Medicine and Emergency Services
dc.contributor.department Clinical Laboratory Services, Diagnostics and Blood Bank
dc.contributor.department Other departments
dc.contributor.school School of Health Sciences


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