deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Nat Commun. 2022 Feb 2;13(1):634. doi: 10.1038/s41467-022-28167-1.
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 = 0.92, P = 1.6 × 10; OR = 0.92, P = 7.2 × 10) 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); 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.
背痛是一种常见且使人虚弱的疾病，其潜在的生物学机制在很大程度上尚不清楚。在这里，我们报告了一项使用临床实践中诊断的背痛全基因组关联研究；背疼（119100 例，909847 例对照）和椎间盘疾病（58854 例，922958 例对照）。我们在 33 个基因座中发现了 41 个变异。最显著的关联（OR=0.92，P=1.6×10；OR=0.92，P=7.2×10）是与 CHST3 基因 3'UTR 区的一个变异（rs1871452-T）相关，该基因编码一种在椎间盘表达的硫酸转移酶。对 IDD 影响最大的是 SLC13A1 基因中罕见（MAF=0.07-0.32%）的功能丧失（LoF）变异，该基因编码一种钠-硫酸盐共转运蛋白（LoF 负担 OR=1.44，P=3.1×10）；这些变异也与血清硫酸盐减少有关。本研究中涉及的基因参与软骨和骨骼生物学以及神经和炎症过程。
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