33 research outputs found
Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBack 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.European Commission
European Commission Joint Research Centre
Novo Nordisk Foundation
Novocure Limite
The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement
The Human Leukocyte Antigen-G 3'UTR 14-bp Deletion is Associated with Poor Survival in an HIV-1-infected Zimbabwean Population
Predictors of hemoglobin in Danish blood donors:results from the Danish Blood Donor Study
The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity:A study of obesity and related metabolic traits among 17,636 Danes
Manhattan plots showing <i>P</i>-values of association of each of the SNPs in the analysis with LPS stimulated plasma cytokine levels.
<p>SNPs are plotted on the X-axis to their position on each chromosome against cytokine levels on the Y-axis (shown as –log<sub>10 </sub><i>P</i>-value).</p