Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
Disease areas:
bones, joints and muscles
Last updated:
Author(s):
Gyda Bjornsdottir, Lilja Stefansdottir, Gudmar Thorleifsson, Patrick Sulem, Kristjan Norland, Egil Ferkingstad, Asmundur Oddsson, Florian Zink, Sigrun H. Lund, Muhammad S. Nawaz, G. Bragi Walters, Astros Th. Skuladottir, Sigurjon A. Gudjonsson, Gudmundur Einarsson, Gisli H. Halldorsson, Valgerdur Bjarnadottir, Gardar Sveinbjornsson, Anna Helgadottir, Unnur Styrkarsdottir, Larus J. Gudmundsson, Ole B. Pedersen, Thomas Folkmann Hansen, Thomas Werge, Karina Banasik, Anders Troelsen, Soren T. Skou, Lise Wegner Thørner, Christian Erikstrup, Kaspar Rene Nielsen, Susan Mikkelsen, Ingileif Jonsdottir, Aron Bjornsson, Ingvar H. Olafsson, Elfar Ulfarsson, Josep Blondal, Arnor Vikingsson, Soren Brunak, Sisse R. Ostrowski, Henrik Ullum, Unnur Thorsteinsdottir, Hreinn Stefansson, Daniel F. Gudbjartsson, Thorgeir E. Thorgeirsson, Kari Stefansson
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.
Aims:To replicate, in a different population, findings from a GWAS in Iceland on lumbar disc disease. For these purposes, we are requesting access to UK…
