TY - JOUR
T1 - Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
AU - DBDS Genetic Consortium
AU - GO Consortium
AU - Bjornsdottir, Gyda
AU - Stefansdottir, Lilja
AU - Thorleifsson, Gudmar
AU - Sulem, Patrick
AU - Norland, Kristjan
AU - Ferkingstad, Egil
AU - Oddsson, Asmundur
AU - Zink, Florian
AU - Lund, Sigrun H.
AU - Nawaz, Muhammad S.
AU - Bragi Walters, G.
AU - Skuladottir, Astros Th
AU - Gudjonsson, Sigurjon A.
AU - Einarsson, Gudmundur
AU - Halldorsson, Gisli H.
AU - Bjarnadottir, Valgerdur
AU - Sveinbjornsson, Gardar
AU - Helgadottir, Anna
AU - Styrkarsdottir, Unnur
AU - Gudmundsson, Larus J.
AU - Pedersen, Ole B.
AU - Hansen, Thomas Folkmann
AU - Werge, Thomas
AU - Banasik, Karina
AU - Troelsen, Anders
AU - Skou, Soren T.
AU - Thørner, Lise Wegner
AU - Erikstrup, Christian
AU - Nielsen, Kaspar Rene
AU - Mikkelsen, Susan
AU - Andersen, Steffen
AU - Brunak, Søren
AU - Burgdorf, Kristoffer
AU - Hjalgrim, Henrik
AU - Jemec, Gregor
AU - Jennum, Poul
AU - Johansson, Per Ingemar
AU - Nyegaard, Mette
AU - Bruun, Mie Topholm
AU - Dinh, Khoa Manh
AU - Sørensen, Erik
AU - Johansson, Pär Ingemar
AU - Gudbjartsson, Daniel
AU - Stefánsson, Hreinn
AU - Þorsteinsdóttir, Unnur
AU - Larsen, Margit Anita Hørup
AU - Didriksen, Maria
AU - Sækmose, Susanne
AU - Zeggini, Eleftheria
AU - Terao, Chikashi
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85123973763
UR - https://www.scopus.com/pages/publications/85123973763#tab=citedBy
U2 - 10.1038/s41467-022-28167-1
DO - 10.1038/s41467-022-28167-1
M3 - Article
C2 - 35110524
AN - SCOPUS:85123973763
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 634
ER -