The association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain. We developed a polygenic risk score (PRS) for “genetic propensity to pain” defined as the number of non-back pain locations (head, face, neck/shoulder, stomach/abdomen, hip, and knee) with duration ≥3 months in 377,538 UK Biobank participants of European ancestry. This PRS was used to stratify TwinsUK MRI samples (n=645) into four strata of genetic propensity to pain. We examined the association between LBP and MRI features of lumbar disc height, disc signal intensity, disc bulge, and osteophytes with adjustments for age, sex, PRS strata, interaction terms for each MRI feature x PRS strata, and twin status.Background
Method
Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied. CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10–7) & genome-wide significant (p<5×10–8) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases.Purpose
Methods
