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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 Agricultural University of Iceland
dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor.author Nielsen, K.R.
dc.contributor.author Pedersen, O.B.
dc.contributor.author Sørensen, E.
dc.contributor.author Ostrowski, S.
dc.contributor.author Johansson, P.I.
dc.contributor.author Gudbjartsson, D.
dc.contributor.author Stefansson, H.
dc.contributor.author Larsen, M.A.H.
dc.contributor.author Didriksen, M.
dc.contributor.author Sækmose, S.
dc.contributor.author Zeggini, E.
dc.contributor.author Hatzikotoulas, K.
dc.contributor.author Southam, L.
dc.contributor.author Gilly, A.
dc.contributor.author Barysenka, A.
dc.contributor.author van Meurs, J.B.J.
dc.contributor.author Boer, C.G.
dc.contributor.author Uitterlinden, A.G.
dc.contributor.author Styrkársdóttir, U.
dc.contributor.author Stefánsdóttir, L.
dc.contributor.author Esko, T.
dc.contributor.author Mägi, R.
dc.contributor.author Teder-Laving, M.
dc.contributor.author Ikegawa, S.
dc.contributor.author Terao, C.
dc.contributor.author Takuwa, H.
dc.contributor.author Meulenbelt, I.
dc.contributor.author Coutinho de Almeida, R.
dc.contributor.author Kloppenburg, M.
dc.contributor.author Tuerlings, M.
dc.contributor.author Slagboom, P.E.
dc.contributor.author Nelissen, R.R.G.H.H.
dc.contributor.author Valdes, A.M.
dc.contributor.author Mangino, M.
dc.contributor.author Tsezou, A.
dc.contributor.author Zengini, E.
dc.contributor.author Alexiadis, G.
dc.contributor.author Babis, G.C.
dc.contributor.author Cheah, K.S.E.
dc.contributor.author Wu, T.T.
dc.contributor.author Samartzis, D.
dc.contributor.author Cheung, J.P.Y.
dc.contributor.author Sham, P.C.
dc.contributor.author Kraft, P.
dc.contributor.author Kang, J.H.
dc.contributor.author Hveem, K.
dc.contributor.author Zwart, J.-A.
dc.contributor.author Luetge, A.
dc.contributor.author Skogholt, A.H.
dc.contributor.author Johnsen, M.B.
dc.contributor.author Thomas, L.F.
dc.contributor.author Winsvold, B.
dc.contributor.author Gabrielsen, M.E.
dc.contributor.author Lee, M.T.M.
dc.contributor.author Zhang, Y.
dc.contributor.author Lietman, S.A.
dc.contributor.author Shivakumar, M.
dc.contributor.author Smith, G.D.
dc.contributor.author Tobias, J.H.
dc.contributor.author Hartley, A.
dc.contributor.author Gaunt, T.R.
dc.contributor.author Zheng, J.
dc.contributor.author Wilkinson, J.M.
dc.contributor.author Steinberg, J.
dc.contributor.author Morris, A.P.
dc.contributor.author Ulfarsson, E.
dc.contributor.author Blondal, J.
dc.contributor.author Brunak, S.
dc.contributor.author Ostrowski, S.R.
dc.contributor.author Ullum, H.
dc.contributor.author Þorsteinsdóttir, U.
dc.contributor.author Stefansson, H.
dc.contributor.author Gudbjartsson, D.F.
dc.contributor.author Thorgeirsson, T.E.
dc.contributor.author Stefansson, K.
dc.contributor.author DBDS Genetic Consortium
dc.contributor.author GO Consortium
dc.date.accessioned 2023-01-25T01:05:24Z
dc.date.available 2023-01-25T01:05:24Z
dc.date.issued 2022-02-02
dc.identifier.citation Nielsen , K R , Pedersen , O B , Sørensen , E , Ostrowski , S , Johansson , P I , Gudbjartsson , D , Stefansson , H , Larsen , M A H , Didriksen , M , Sækmose , S , Zeggini , E , Hatzikotoulas , K , Southam , L , Gilly , A , Barysenka , A , van Meurs , J B J , Boer , C G , Uitterlinden , A G , Styrkársdóttir , U , Stefánsdóttir , L , Esko , T , Mägi , R , Teder-Laving , M , Ikegawa , S , Terao , C , Takuwa , H , Meulenbelt , I , Coutinho de Almeida , R , Kloppenburg , M , Tuerlings , M , Slagboom , P E , Nelissen , R R G H H , Valdes , A M , Mangino , M , Tsezou , A , Zengini , E , Alexiadis , G , Babis , G C , Cheah , K S E , Wu , T T , Samartzis , D , Cheung , J P Y , Sham , P C , Kraft , P , Kang , J H , Hveem , K , Zwart , J-A , Luetge , A , Skogholt , A H , Johnsen , M B , Thomas , L F , Winsvold , B , Gabrielsen , M E , Lee , M T M , Zhang , Y , Lietman , S A , Shivakumar , M , Smith , G D , Tobias , J H , Hartley , A , Gaunt , T R , Zheng , J , Wilkinson , J M , Steinberg , J , Morris , A P , Ulfarsson , E , Blondal , J , Brunak , S , Ostrowski , S R , Ullum , H , Þorsteinsdóttir , U , Stefansson , H , Gudbjartsson , D F , Thorgeirsson , T E , Stefansson , K , 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 , pp. 634 . https://doi.org/10.1038/s41467-022-28167-1
dc.identifier.issn 2041-1723
dc.identifier.other 72660178
dc.identifier.other a24b2b17-b60a-4660-b4a6-09053fbbec5e
dc.identifier.other ORCID: /0000-0002-3806-2296/work/123415627
dc.identifier.other 85123973763
dc.identifier.other 35110524
dc.identifier.other unpaywall: 10.1038/s41467-022-28167-1
dc.identifier.uri https://hdl.handle.net/20.500.11815/3898
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 2337466
dc.format.extent 634
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 Bone and Bones/metabolism
dc.subject Intervertebral Disc/metabolism
dc.subject Humans
dc.subject Symporters/genetics
dc.subject Sodium Sulfate Cotransporter/genetics
dc.subject Sulfates/metabolism
dc.subject Intervertebral Disc Degeneration/genetics
dc.subject Intervertebral Disc Displacement/genetics
dc.subject 3' Untranslated Regions
dc.subject General Physics and Astronomy
dc.subject General Chemistry
dc.subject General Biochemistry,Genetics and Molecular Biology
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.doi 10.1038/s41467-022-28167-1
dc.relation.url http://www.scopus.com/inward/record.url?eid=2-s2.0-85123973763&partnerID=MN8TOARS
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 Physical Sciences
dc.contributor.department Faculty of Medicine
dc.contributor.department Women's and Childrens's Services
dc.contributor.department Faculty of Industrial Engineering, Mechanical Engineering and Computer Science
dc.contributor.department Department of Engineering
dc.contributor.department Internal Medicine and Emergency Services
dc.contributor.department Faculty of Food Science and Nutrition
dc.contributor.department Other departments
dc.contributor.school Health Sciences
dc.contributor.school School of Health Sciences


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