Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
Copyright policy )Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
AbstractBack 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.
- Aalborg University Denmark
- University of Southern Denmark Denmark
- University of Copenhagen Denmark
- University of Iceland Iceland
- Copenhagen Business School Denmark
Symporters/genetics, Symporters, Sulfates, Science, Q, Intervertebral Disc/metabolism, Intervertebral Disc Degeneration, Bone and Bones/metabolism, Article, Bone and Bones, Intervertebral Disc Degeneration/genetics, Intervertebral Disc Displacement/genetics, Sulfates/metabolism, Humans, Sodium Sulfate Cotransporter/genetics, Intervertebral Disc, 3' Untranslated Regions, Intervertebral Disc Displacement, Genome-Wide Association Study, Sodium Sulfate Cotransporter
Symporters/genetics, Symporters, Sulfates, Science, Q, Intervertebral Disc/metabolism, Intervertebral Disc Degeneration, Bone and Bones/metabolism, Article, Bone and Bones, Intervertebral Disc Degeneration/genetics, Intervertebral Disc Displacement/genetics, Sulfates/metabolism, Humans, Sodium Sulfate Cotransporter/genetics, Intervertebral Disc, 3' Untranslated Regions, Intervertebral Disc Displacement, Genome-Wide Association Study, Sodium Sulfate Cotransporter
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