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

TY - JOUR

T1 - The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain

AU - Suri, Pradeep

AU - Naeini, Maryam Kazemi

AU - Heagerty, Patrick J.

AU - Freidin, Maxim B.

AU - Smith, Isabelle Granville

AU - Elgaeva, Elizaveta E.

AU - Compte, Roger

AU - Tsepilov, Yakov A.

AU - Williams, Frances M.K.

N1 - Publisher Copyright: © 2024

PY - 2025/1

Y1 - 2025/1

N2 - BACKGROUND CONTEXTAssociations 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.PURPOSETo examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.STUDY DESIGNCross-sectional study in UK Biobank (UKB) and Twins UK.PATIENT SAMPLESA 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 MEASURESEver having had LBP associated with disability lasting ≥1 month (LBP1).METHODSUsing 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.RESULTSIn 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).CONCLUSIONSGenetically-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.

AB - BACKGROUND CONTEXTAssociations 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.PURPOSETo examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.STUDY DESIGNCross-sectional study in UK Biobank (UKB) and Twins UK.PATIENT SAMPLESA 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 MEASURESEver having had LBP associated with disability lasting ≥1 month (LBP1).METHODSUsing 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.RESULTSIn 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).CONCLUSIONSGenetically-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.

KW - Epidemiology

KW - Genetics

KW - Intervertebral disc

KW - Low back pain

KW - Patient stratification

KW - Polygenic risk score

UR - http://www.scopus.com/inward/record.url?scp=85199477844&partnerID=8YFLogxK

U2 - 10.1016/j.spinee.2024.05.018

DO - 10.1016/j.spinee.2024.05.018

M3 - Article

C2 - 38942297

AN - SCOPUS:85199477844

SN - 1529-9430

VL - 25

SP - 8

EP - 17

JO - Spine Journal

JF - Spine Journal

IS - 1

ER -