Ερευνητικό υλικό ΕΚΠΑ

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

Αγγλικά

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).

2022

Bjornsdottir, G.
Stefansdottir, L.
Thorleifsson, G.
Sulem, P.
Norland, K.
Ferkingstad, E.
Oddsson, A.
Zink, F.
Lund, S.H.
Nawaz, M.S.
Bragi Walters, G.
Skuladottir, A.T.
Gudjonsson, S.A.
Einarsson, G.
Halldorsson, G.H.
Bjarnadottir, V.
Sveinbjornsson, G.
Helgadottir, A.
Styrkarsdottir, U.
Gudmundsson, L.J.
Pedersen, O.B.
Hansen, T.F.
Werge, T.
Banasik, K.
Troelsen, A.
Skou, S.T.
Thørner, L.W.
Erikstrup, C.
Nielsen, K.R.
Mikkelsen, S.
Andersen, S.
Brunak, S.
Burgdorf, K.
Hjalgrim, H.
Jemec, G.
Jennum, P.
Johansson, P.I.
Nielsen, K.R.
Nyegaard, M.
Bruun, M.T.
Pedersen, O.B.
Dinh, K.M.
Sørensen, E.
Ostrowski, S.
Johansson, P.I.
Gudbjartsson, D.
Stefánsson, H.
Þorsteinsdóttir, U.
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.
Jonsson, H.
Ingvarsson, T.
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.
Jonsdottir, I.
Bjornsson, A.
Olafsson, I.H.
Ulfarsson, E.
Blondal, J.
Vikingsson, A.
Brunak, S.
Ostrowski, S.R.
Ullum, H.
Thorsteinsdottir, U.
Stefansson, H.
Gudbjartsson, D.F.
Thorgeirsson, T.E.
Stefansson, K.
DBDS Genetic Consortium
GO Consortium

Nature Communications

Institute of Geographic Sciences and Natural Resources Research

13

1

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

https://doi.org/10.1038/s41467-022-28167-1

10.1038/s41467-022-28167-1

https://pergamos.lib.uoa.gr/uoa/dl/object/3025446