| Title: | The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain |
| Journal: | The Spine Journal |
| Published: | 26 Jun 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38942297/ |
| DOI: | https://doi.org/10.1016/j.spinee.2024.05.018 |
Publication 11791
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Abstract
BACKGROUND CONTEXT: 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.</p>
PURPOSE: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.</p>
STUDY DESIGN: Cross-sectional study in UK Biobank (UKB) and Twins UK.</p>
PATIENT SAMPLES: 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.</p>
OUTCOME MEASURES: Ever having had LBP associated with disability lasting ≥1 month (LBP1).</p>
METHODS: 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.</p>
RESULTS: 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=2.6×10-6), 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).</p>
CONCLUSIONS: 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.</p>
9 Authors
- Pradeep Suri
- Maryam Kazemi Naeini
- Patrick J Heagerty
- Maxim B Freidin
- Isabelle Granville Smith
- Elizaveta E Elgaeva
- Roger Compte
- Yakov A Tsepilov
- Frances M K Williams
1 Application
| Application ID | Title |
|---|---|
| 18219 | Genetic and epidemiological analyses of low back pain |
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