The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain

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

doi:10.1016/j.spinee.2024.05.018

The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain

Spine J. 2025 Jan;25(1):8-17. doi: 10.1016/j.spinee.2024.05.018. Epub 2024 Jun 26.

Authors

Pradeep Suri¹, Maryam Kazemi Naeini², Patrick J Heagerty³, Maxim B Freidin⁴, Isabelle Granville Smith², Elizaveta E Elgaeva⁵, Roger Compte², Yakov A Tsepilov⁶, Frances M K Williams²

Affiliations

¹ 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. Electronic address: pradeep.suri@va.gov.
² Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.
³ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
⁴ Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK; Department of Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
⁵ Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.
⁶ Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk, Russia; Wellcome Sanger Institute, Cambridge, UK.

PMID: 38942297
PMCID: PMC11637947 (available on 2026-01-01)
DOI: 10.1016/j.spinee.2024.05.018

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.

Purpose: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.

Study design: Cross-sectional study in UK Biobank (UKB) and Twins UK.

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.

Outcome measures: Ever having had LBP associated with disability lasting ≥1 month (LBP1).

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.

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).

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.

Keywords: Epidemiology; Genetics; Intervertebral disc; Low back pain; Patient stratification; Polygenic risk score.

Published by Elsevier Inc.

Publication types

Twin Study

MeSH terms

Adult
Aged
Cross-Sectional Studies
Female
Genetic Predisposition to Disease*
Genome-Wide Association Study*
Humans
Intervertebral Disc Degeneration* / diagnostic imaging
Intervertebral Disc Degeneration* / genetics
Low Back Pain* / diagnostic imaging
Low Back Pain* / genetics
Lumbar Vertebrae* / diagnostic imaging
Magnetic Resonance Imaging
Male
Middle Aged

Grants and funding

P30 AR072572/AR/NIAMS NIH HHS/United States