Rare SLC13A1 Variants Associate with Intervertebral Disc Disorder Highlighting Role of Sulfate in Disc Pathology

Gyda Bjornsdottir*, Lilja Stefansdottir, Gudmar Thorleifsson, Patrick Sulem, Kristjan Norland, Egil Ferkingstad, Asmundur Oddsson, Florian Zink, Sigrun H. Lund, Muhammad S. Nawaz, Walters G. Bragi, Astros Th. Skuladottir, Larus J. Gudmundsson, Ole B. Pedersen, Thomas Folkmann Hansen, Thomas Werge, Karina Banasik, Anders Troelsen, Søren T. Skou, Lise Wegner ThørnerChristian Erikstrup, Kaspar René Nielsen, Susan Mikkelsen, Steffen Andersen, Søren Brunak, Kristoffer Sølvsten Burgdorf, Henrik Hjalgrim, Gregot Jemec, Poul Jennum, Per Ingemar Johansson, Rene Kasper Nielsen, Mette Nyegaard, Mie Topholm Bruun, Khoa Manh Dinh, Erik Sørensen, Sisse Rye Ostrowski, Pär Ingemar Johansson, Daniel F. Gudbjartsson, Hreinn Stefansson, Unnur Thorsteinsdottir, Margit Anita Hørup Larsen, Maria Didriksen, Susanne Sækmose, Eleftheria Zeggini, Konstantinos Hatzikotoulas, Lorraine Southam, Arthur Gilly, Joyce B. J. van Meurs, Cindy G. Boer, André G. Uitterlinden, Helgi Jonsson, Thorvaldur Ingvarsson, Tõnu Esko, Reedik Mägi, Maris Teder-Laving, Shiro Ikegawa, Chikashi Terao, Hiroshi Takuwa, Ingrid Meulenbelt, Rodrigo Coutinho de Almeida, Margreet Kloppenburg, Margo Tuerlings, P. Eline Slagboom, Rob R. G. H. H. Nelissen, Ana M. Valdes, Massimo Mangino, Aspasia Tsezou, Eleni Zengini, George Alexiadis, George C. Babis, Kathryn S. E. Cheah, Tian T. Wu, Dino Samartzis, Pak Chung Sham, Peter Kraft, Jae Hee Kang, Kristian Hveem, John-Anker Zwart, Almut Lütge, Anne Heidi Skogholt, Marianne B. Johnsen, Laurent F. Thomas, Bendik Winsvold, Maiken E. Gabrielsen, Ming Ta Michael Lee, Yanfei Zhang, Steven A. Lietman, Manu Shivakumar, George Davey Smith, Jonathan H. Tobias, April Hartley, Tom R. Gaunt, Jie Zheng, J. Mark Wilkinson, Julia Steinberg, Andrew P. Morris, Ingileif Jonsdottir, Aron Bjornsson, Ingvar H. Olafsson, Elfar Ulfarsson, Josep Blondal, Arnor Vikingsson, Sisse Rye Ostrowski, Henrik Ullum, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Thorgeir E. Thorgeirsson*, Kari Stefansson*, DBDS Genetic Consortium, GO Consortium

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

48 Downloads (Pure)

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
Original languageEnglish
Article number634
JournalNature Communications
Volume13
Issue number1
Number of pages13
DOIs
Publication statusPublished - 1 Dec 2022

Cite this