Brain-specific genes contribute to chronic but not to acute back pain.

IF 3.4 Q2 NEUROSCIENCES
Andrey V Bortsov, Marc Parisien, Samar Khoury, Amy E Martinsen, Marie Udnesseter Lie, Ingrid Heuch, Kristian Hveem, John-Anker Zwart, Bendik S Winsvold, Luda Diatchenko
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引用次数: 11

Abstract

Introduction: Back pain is the leading cause of disability worldwide. Although most back pain cases are acute, 20% of acute pain patients experience chronic back pain symptoms. It is unclear whether acute pain and chronic pain have similar or distinct underlying genetic mechanisms.

Objectives: To characterize the molecular and cellular pathways contributing to acute and chronic pain states.

Methods: Cross-sectional observational genome-wide association study.

Results: A total of 375,158 individuals from the UK Biobank cohort were included in the discovery of genome-wide association study. Of those, 70,633 (19%) and 32,209 (9%) individuals met the definition of chronic and acute back pain, respectively. A total of 355 single nucleotide polymorphism grouped into 13 loci reached the genome-wide significance threshold (5x10-8) for chronic back pain, but none for acute. Of these, 7 loci were replicated in the Nord-Trøndelag Health Study (HUNT) cohort (19,760 chronic low back pain cases and 28,674 pain-free controls). Single nucleotide polymorphism heritability was 4.6% (P=1.4x10-78) for chronic back pain and 0.81% (P=1.4x10-8) for acute back pain. Similar differences in heritability estimates between acute and chronic back pain were found in the HUNT cohort: 3.4% (P=0.0011) and 0.6% (P=0.851), respectively. Pathway analyses, tissue-specific heritability enrichment analyses, and epigenetic characterization suggest a substantial genetic contribution to chronic but not acute back pain from the loci predominantly expressed in the central nervous system.

Conclusion: Chronic back pain is substantially more heritable than acute back pain. This heritability is mostly attributed to genes expressed in the brain.

Abstract Image

Abstract Image

Abstract Image

大脑特异性基因会导致慢性背痛,但不会导致急性背痛。
简介:背痛是世界范围内致残的主要原因。虽然大多数背痛病例是急性的,但20%的急性疼痛患者会出现慢性背痛症状。目前尚不清楚急性疼痛和慢性疼痛是否具有相似或不同的潜在遗传机制。目的:表征导致急性和慢性疼痛状态的分子和细胞通路。方法:横断面观察性全基因组关联研究。结果:来自UK Biobank队列的375158个个体被纳入全基因组关联研究的发现。其中,70,633人(19%)和32,209人(9%)分别符合慢性和急性背痛的定义。分为13个位点的355个单核苷酸多态性在慢性背痛中达到全基因组显著阈值(5x10-8),但在急性背痛中没有。其中,7个基因座在north - tr øndelag健康研究(HUNT)队列(19760例慢性腰痛患者和28674例无痛对照)中得到了重复。慢性背痛的单核苷酸多态性遗传率为4.6% (P=1.4 × 10-78),急性背痛的单核苷酸多态性遗传率为0.81% (P=1.4 × 10-8)。在HUNT队列中,急性和慢性背痛的遗传力估计也存在类似差异:分别为3.4% (P=0.0011)和0.6% (P=0.851)。通路分析、组织特异性遗传富集分析和表观遗传学表征表明,中枢神经系统中主要表达的位点对慢性而非急性背痛有重要的遗传贡献。结论:慢性背痛比急性背痛更容易遗传。这种遗传性主要归因于大脑中表达的基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pain Reports
Pain Reports Medicine-Anesthesiology and Pain Medicine
CiteScore
7.50
自引率
2.10%
发文量
93
审稿时长
8 weeks
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