deCODE genetics/Amgen Inc., Reykjavik, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Nat Commun. 2022 Mar 24;13(1):1598. doi: 10.1038/s41467-022-29133-7.
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
腕管综合征（CTS）是最常见的嵌压性神经病，其潜在的生物学机制很大程度上尚未被阐明。在一项针对 CTS 的全基因组关联研究（48843 例病例和 1190837 例对照）中，我们在 50 个位点发现了与该综合征相关的 53 个序列变异。与 CTS 相关的最显著关联是丝氨酸蛋白酶抑制剂 A1（SERPINA1）中的错义变异（p.Glu366Lys），该变异可保护机体免受 CTS 影响（P=2.9×10-8，OR=0.76）。通过各种功能分析，我们得出结论，至少有 22 个基因介导 CTS 风险，并强调了 19 个 CTS 变异在细胞外基质生物学中的作用。我们发现，双侧/复发性/持续性病例的遗传风险比非复发性/非持续性病例更高。除了早期激素替代疗法、骨关节炎和不安腿综合征外，身高和 BMI 等人体测量特征与 CTS 也存在遗传相关性。我们的研究结果表明，细胞外基质的成分在 CTS 的发病机制中起着关键作用。
