%0 Journal Article
%T The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain.
%A Suri P
%A Naeini MK
%A Heagerty PJ
%A Freidin MB
%A Smith IG
%A Elgaeva EE
%A Compte R
%A Tsepilov YA
%A Williams FMK
%J Spine J
%V 0
%N 0
%D 2024 Jun 26
%M 38942297
%F 4.297
%R 10.1016/j.spinee.2024.05.018
%X <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.<BR><B>METHODS: </B>Cross-sectional study in UK Biobank (UKB) and TwinsUK.<BR><B>METHODS: </B>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.<BR><B>METHODS: </B>Ever having had LBP associated with disability lasting ≥1 month (LBP1).<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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=0.002), with small-magnitude and/or non-significant associations in the lowest two PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤0.05).<BR><B>CONCLUSIONS: </B>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.