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

DBDS Genetic Consortium, Gyda Bjornsdottir*, Lilja Stefansdottir, Ole B Pedersen, Soren T Skou, Kari Stefansson*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

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.

OriginalsprogEngelsk
Sider (fra-til)634
TidsskriftNature communications
Vol/bind13
Udgave nummer1
DOI
StatusUdgivet - 2 feb. 2022

Bibliografisk note

© 2022. The Author(s).

Fingeraftryk

Udforsk hvilke forskningsemner 'Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology' indeholder.

Citationsformater