@article{3025446,
    title = "Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology",
    author = "Bjornsdottir, G. and Stefansdottir, L. and Thorleifsson, G. and Sulem, P. and Norland, K. and Ferkingstad, E. and Oddsson, A. and Zink, F. and Lund, S.H. and Nawaz, M.S. and Bragi Walters, G. and Skuladottir, A.T. and Gudjonsson, S.A. and Einarsson, G. and Halldorsson, G.H. and Bjarnadottir, V. and Sveinbjornsson, G. and Helgadottir, A. and Styrkarsdottir, U. and Gudmundsson, L.J. and Pedersen, O.B. and Hansen, T.F. and Werge, T. and Banasik, K. and Troelsen, A. and Skou, S.T. and Thørner, L.W. and Erikstrup, C. and Nielsen, K.R. and Mikkelsen, S. and Andersen, S. and Brunak, S. and Burgdorf, K. and Hjalgrim, H. and Jemec, G. and Jennum, P. and Johansson, P.I. and Nielsen, K.R. and Nyegaard, M. and Bruun, M.T. and Pedersen, O.B. and Dinh, K.M. and Sørensen, E. and Ostrowski, S. and Johansson, P.I. and Gudbjartsson, D. and Stefánsson, H. and Þorsteinsdóttir, U. and Larsen, M.A.H. and Didriksen, M. and Sækmose, S. and Zeggini, E. and Hatzikotoulas, K. and Southam, L. and Gilly, A. and Barysenka, A. and van Meurs, J.B.J. and Boer, C.G. and Uitterlinden, A.G. and Styrkársdóttir, U. and Stefánsdóttir, L. and Jonsson, H. and Ingvarsson, T. and Esko, T. and Mägi, R. and Teder-Laving, M. and Ikegawa, S. and Terao, C. and Takuwa, H. and Meulenbelt, I. and Coutinho de Almeida, R. and Kloppenburg, M. and Tuerlings, M. and Slagboom, P.E. and Nelissen, R.R.G.H.H. and Valdes, A.M. and Mangino, M. and Tsezou, A. and Zengini, E. and Alexiadis, G. and Babis, G.C. and Cheah, K.S.E. and Wu, T.T. and Samartzis, D. and Cheung, J.P.Y. and Sham, P.C. and Kraft, P. and Kang, J.H. and Hveem, K. and Zwart, J.-A. and Luetge, A. and Skogholt, A.H. and Johnsen, M.B. and Thomas, L.F. and Winsvold, B. and Gabrielsen, M.E. and Lee, M.T.M. and Zhang, Y. and Lietman, S.A. and Shivakumar, M. and Smith, G.D. and Tobias, J.H. and Hartley, A. and Gaunt, T.R. and Zheng, J. and Wilkinson, J.M. and Steinberg, J. and Morris, A.P. and Jonsdottir, I. and Bjornsson, A. and Olafsson, I.H. and Ulfarsson, E. and Blondal, J. and Vikingsson, A. and Brunak, S. and Ostrowski, S.R. and Ullum, H. and Thorsteinsdottir, U. and Stefansson, H. and Gudbjartsson, D.F. and Thorgeirsson, T.E. and Stefansson, K. and DBDS Genetic Consortium and GO Consortium",
    journal = "Nature Communications",
    year = "2022",
    volume = "13",
    number = "1",
    publisher = "Institute of Geographic Sciences and Natural Resources Research",
    issn = "2041-1723",
    doi = "10.1038/s41467-022-28167-1",
    keywords = "disability;  gene;  gene expression;  pathology;  serum;  sulfate, cotransporter;  SLC13A1 protein, human;  sodium sulfate;  sulfate, 3' untranslated region;  bone;  genetics;  genome-wide association study;  human;  intervertebral disk;  intervertebral disk degeneration;  intervertebral disk hernia;  metabolism, 3' Untranslated Regions;  Bone and Bones;  Genome-Wide Association Study;  Humans;  Intervertebral Disc;  Intervertebral Disc Degeneration;  Intervertebral Disc Displacement;  Sodium Sulfate Cotransporter;  Sulfates;  Symporters",
    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. © 2022, The Author(s)."
}