Suri Pradeep, Naeini Maryam Kazemi, Heagerty Patrick J, Freidin Maxim B, Smith Isabelle Granville, Elgaeva Elizaveta E, Compte Roger, Tsepilov Yakov A, Williams Frances M K
Division of Rehabilitation Care Services, VA Puget Sound Health Care System, Washington, USA; Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, Washington, USA; Department of Rehabilitation Medicine, University of Washington, Seattle, Washington, USA; Clinical Learning, Evidence, and Research (CLEAR) Center, University of Washington, Seattle, Washington, USA.
Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.
Spine J. 2025 Jan;25(1):8-17. doi: 10.1016/j.spinee.2024.05.018. Epub 2024 Jun 26.
Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.
To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.
Cross-sectional study in UK Biobank (UKB) and Twins UK.
A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.
Ever having had LBP associated with disability lasting ≥1 month (LBP1).
Using the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.
In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4-2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR=2.5 [95% CI 1.7-3.7], p=2.6×10), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=.002), with small-magnitude and/or nonsignificant associations in the lowest 2 PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤.05).
Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.
磁共振成像（MRI）检测到的腰椎间盘退变（LDD）与腰痛（LBP）之间的关联通常程度适中。这种关联在特定患者亚组中可能更强。
研究LDD与LBP之间的关联是否会因潜在的疼痛遗传易感性而改变。
在英国生物银行（UKB）和英国双胞胎队列（Twins UK）中进行的横断面研究。
对347,538名UKB参与者进行了全基因组关联研究（GWAS），以分析解剖学慢性疼痛部位的数量。该GWAS用于在30,000名UKB参与者的保留样本中开发全基因组多基因风险评分（PRS）。然后，将PRS模型用于对645名接受标准化LDD MRI评估的TwinsUK参与者进行分析。
曾患伴有持续≥1个月残疾的腰痛（LBP1）。
使用PRS作为“遗传预测的疼痛易感性”的代理指标，我们将TwinsUK参与者分为PRS四分位数。一个“基本”模型研究了LDD汇总评分（LSUM）与LBP1之间的关联，并对协变量进行了调整。一个“完全调整”模型还对PRS四分位数和LSUM×PRS四分位数交互项进行了调整。
在基本模型中，LSUM每增加一个标准差，LBP1的比值比（OR）为1.8（95%置信区间[CI] 1.4 - 2.3）。在完全调整模型中，在PRS四分位数4（最高的PRS四分位数）中存在统计学上显著的LSUM - LBP1关联（OR = 2.5 [95% CI 1.7 - 3.7]，p = 2.6×10），在四分位数3中也存在关联（OR = 2.0，[95% CI 1.3 - 3.0]；p =.002），而在最低的2个PRS四分位数中关联程度较小和/或不显著。PRS四分位数是LSUM - LBP1关联的显著效应修饰因素（交互作用p≤.05）。
遗传预测的疼痛易感性改变了LDD与LBP之间的关联，在遗传疼痛易感性最高的人群中关联最强。腰椎MRI检查结果在特定亚组人群中可能与LBP有更强的联系。
