剖析慢性背痛的遗传背景。

Decomposing the genetic background of chronic back pain.

作者信息

Elgaeva Elizaveta E, Zorkoltseva Irina V, Nostaeva Arina V, Verzun Dmitrii A, Tiys Evgeny S, Timoshchuk Anna N, Kirichenko Anatoliy V, Svishcheva Gulnara R, Freidin Maxim B, Williams Frances M K, Suri Pradeep, Aulchenko Yurii S, Axenovich Tatiana I, Tsepilov Yakov A

机构信息

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10, Ac. Lavrentieva ave., 630090, Novosibirsk, Russia.

Novosibirsk State University, 1, Pirogova str., 630090, Novosibirsk, Russia.

出版信息

Hum Mol Genet. 2025 Apr 6;34(8):711-725. doi: 10.1093/hmg/ddae195.

DOI:10.1093/hmg/ddae195

PMID:39895344

Abstract

Chronic back pain (CBP) is a disabling condition with a lifetime prevalence of 40% and a substantial socioeconomic burden. Because of the high heterogeneity of CBP, subphenotyping may help to improve prediction and support personalized treatment of CBP. To investigate CBP subphenotypes, we decomposed its genetic background into a shared one common to other chronic pain conditions (back, neck, hip, knee, stomach, and head pain) and unshared genetic background specific to CBP. We identified and replicated 18 genes with shared impact across different chronic pain conditions and two genes that were specific for CBP. Among people with CBP, we demonstrated that polygenic risk scores accounting for the shared and unshared genetic backgrounds of CBP may underpin different CBP subphenotypes. These subphenotypes are characterized by varying genetic predisposition to diverse medical conditions and interventions such as diabetes mellitus, myocardial infarction, diagnostic endoscopic procedures, and surgery involving muscles, bones, and joints.

摘要

慢性背痛（CBP）是一种致残性疾病，终生患病率为40%，并带来巨大的社会经济负担。由于CBP的高度异质性，亚表型分析可能有助于改善预测并支持CBP的个性化治疗。为了研究CBP亚表型，我们将其遗传背景分解为与其他慢性疼痛疾病（背部、颈部、臀部、膝盖、胃部和头部疼痛）共有的一个以及CBP特有的非共享遗传背景。我们鉴定并重复验证了18个在不同慢性疼痛疾病中具有共同影响的基因以及两个CBP特有的基因。在患有CBP的人群中，我们证明，考虑CBP共享和非共享遗传背景的多基因风险评分可能是不同CBP亚表型的基础。这些亚表型的特征是对多种医疗状况和干预措施（如糖尿病、心肌梗死、诊断性内镜检查以及涉及肌肉、骨骼和关节的手术）具有不同的遗传易感性。