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

Almenn færsla
dc.contributorAgricultural University of Iceland
dc.contributor.authorNielsen, K.R.
dc.contributor.authorPedersen, O.B.
dc.contributor.authorSørensen, E.
dc.contributor.authorOstrowski, S.
dc.contributor.authorJohansson, P.I.
dc.contributor.authorGudbjartsson, D.
dc.contributor.authorStefansson, H.
dc.contributor.authorLarsen, M.A.H.
dc.contributor.authorDidriksen, M.
dc.contributor.authorSækmose, S.
dc.contributor.authorZeggini, E.
dc.contributor.authorHatzikotoulas, K.
dc.contributor.authorSoutham, L.
dc.contributor.authorGilly, A.
dc.contributor.authorBarysenka, A.
dc.contributor.authorvan Meurs, J.B.J.
dc.contributor.authorBoer, C.G.
dc.contributor.authorUitterlinden, A.G.
dc.contributor.authorStyrkársdóttir, U.
dc.contributor.authorStefánsdóttir, L.
dc.contributor.authorEsko, T.
dc.contributor.authorMägi, R.
dc.contributor.authorTeder-Laving, M.
dc.contributor.authorIkegawa, S.
dc.contributor.authorTerao, C.
dc.contributor.authorTakuwa, H.
dc.contributor.authorMeulenbelt, I.
dc.contributor.authorCoutinho de Almeida, R.
dc.contributor.authorKloppenburg, M.
dc.contributor.authorTuerlings, M.
dc.contributor.authorSlagboom, P.E.
dc.contributor.authorNelissen, R.R.G.H.H.
dc.contributor.authorValdes, A.M.
dc.contributor.authorMangino, M.
dc.contributor.authorTsezou, A.
dc.contributor.authorZengini, E.
dc.contributor.authorAlexiadis, G.
dc.contributor.authorBabis, G.C.
dc.contributor.authorCheah, K.S.E.
dc.contributor.authorWu, T.T.
dc.contributor.authorSamartzis, D.
dc.contributor.authorCheung, J.P.Y.
dc.contributor.authorSham, P.C.
dc.contributor.authorKraft, P.
dc.contributor.authorKang, J.H.
dc.contributor.authorHveem, K.
dc.contributor.authorZwart, J.-A.
dc.contributor.authorLuetge, A.
dc.contributor.authorSkogholt, A.H.
dc.contributor.authorJohnsen, M.B.
dc.contributor.authorThomas, L.F.
dc.contributor.authorWinsvold, B.
dc.contributor.authorGabrielsen, M.E.
dc.contributor.authorLee, M.T.M.
dc.contributor.authorZhang, Y.
dc.contributor.authorLietman, S.A.
dc.contributor.authorShivakumar, M.
dc.contributor.authorSmith, G.D.
dc.contributor.authorTobias, J.H.
dc.contributor.authorHartley, A.
dc.contributor.authorGaunt, T.R.
dc.contributor.authorZheng, J.
dc.contributor.authorWilkinson, J.M.
dc.contributor.authorSteinberg, J.
dc.contributor.authorMorris, A.P.
dc.contributor.authorUlfarsson, E.
dc.contributor.authorBlondal, J.
dc.contributor.authorBrunak, S.
dc.contributor.authorOstrowski, S.R.
dc.contributor.authorUllum, H.
dc.contributor.authorÞorsteinsdóttir, U.
dc.contributor.authorStefansson, H.
dc.contributor.authorGudbjartsson, D.F.
dc.contributor.authorThorgeirsson, T.E.
dc.contributor.authorStefansson, K.
dc.contributor.authorDBDS Genetic Consortium
dc.contributor.authorGO Consortium
dc.date.accessioned2025-09-22T12:49:09Z
dc.date.available2025-09-22T12:49:09Z
dc.date.issued2022-02-02
dc.descriptionFunding 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).en
dc.description.abstractBack 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.en
dc.description.versionPeer revieweden
dc.format.extent2337466
dc.format.extent634
dc.identifier.citationNielsen, 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/s41467-022-28167-1en
dc.identifier.doi10.1038/s41467-022-28167-1
dc.identifier.issn2041-1723
dc.identifier.other72660178
dc.identifier.othera24b2b17-b60a-4660-b4a6-09053fbbec5e
dc.identifier.otherORCID: /0000-0002-3806-2296/work/123415627
dc.identifier.other85123973763
dc.identifier.other35110524
dc.identifier.otherunpaywall: 10.1038/s41467-022-28167-1
dc.identifier.urihttps://hdl.handle.net/20.500.11815/5606
dc.language.isoen
dc.relation.ispartofseriesNature Communications; 13(1)en
dc.relation.urlhttps://www.scopus.com/pages/publications/85123973763en
dc.relation.urlhttps://www.scopus.com/pages/publications/85123973763en
dc.rightsinfo:eu-repo/semantics/openAccessen
dc.subjectIntervertebral Disc Degenerationen
dc.subjectIntervertebral Disc Displacementen
dc.subjectBack Painen
dc.subjectGenome-Wide Association Studyen
dc.subjectBone and Bones/metabolismen
dc.subjectIntervertebral Disc/metabolismen
dc.subjectHumansen
dc.subjectSymporters/geneticsen
dc.subjectSodium Sulfate Cotransporter/geneticsen
dc.subjectSulfates/metabolismen
dc.subjectIntervertebral Disc Degeneration/geneticsen
dc.subjectIntervertebral Disc Displacement/geneticsen
dc.subject3' Untranslated Regionsen
dc.subjectGeneral Physics and Astronomyen
dc.subjectGeneral Chemistryen
dc.subjectGeneral Biochemistry,Genetics and Molecular Biologyen
dc.titleRare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathologyen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/articleen

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