학술논문
Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
Document Type
Original Paper
Author
Bjornsdottir, Gyda; Stefansdottir, Lilja; Thorleifsson, Gudmar; Sulem, Patrick; Norland, Kristjan; Ferkingstad, Egil; Oddsson, Asmundur; Zink, Florian; Lund, Sigrun H.; Nawaz, Muhammad S.; Bragi Walters, G.; Skuladottir, Astros Th.; Gudjonsson, Sigurjon A.; Einarsson, Gudmundur; Halldorsson, Gisli H.; Bjarnadottir, Valgerdur; Sveinbjornsson, Gardar; Helgadottir, Anna; Styrkarsdottir, Unnur; Gudmundsson, Larus J.; Pedersen, Ole B.; Hansen, Thomas Folkmann; Werge, Thomas; Banasik, Karina; Troelsen, Anders; Skou, Soren T.; Thørner, Lise Wegner; Erikstrup, Christian; Nielsen, Kaspar Rene; Mikkelsen, Susan; Jonsdottir, Ingileif; Bjornsson, Aron; Olafsson, Ingvar H.; Ulfarsson, Elfar; Blondal, Josep; Vikingsson, Arnor; Brunak, Soren; Ostrowski, Sisse R.; Ullum, Henrik; Thorsteinsdottir, Unnur; Stefansson, Hreinn; Gudbjartsson, Daniel F.; Thorgeirsson, Thorgeir E.; Stefansson, Kari
Source
Nature Communications. 13(1)
Subject
Language
English
ISSN
2041-1723
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.
Little is known about the biology of back pain, a leading cause of disability. Here the authors report 30 new back pain loci, implicating genes involved in cartilage/bone biology, as well as neurological and inflammatory processes.
Little is known about the biology of back pain, a leading cause of disability. Here the authors report 30 new back pain loci, implicating genes involved in cartilage/bone biology, as well as neurological and inflammatory processes.