Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 35110524.
- Also identified by DOI 10.1038/s41467-022-28167-1 and PMC identifier 8810832.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (OR<sub>IDD</sub> = 0.92, P = 1.6 × 10<sup>-39</sup>; OR<sub>dorsalgia</sub> = 0.92, P = 7.2 × 10<sup>-15</sup>) 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<sup>-11</sup>); 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.
Medical subject headings
- Intervertebral Disc
- Intervertebral Disc Degeneration
- Intervertebral Disc Displacement
- Sodium Sulfate Cotransporter
- Sulfates