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Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.

ABSTRACT: Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD.We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2.This study of 4600 individuals identified four single nucleotide polymorphisms with p<5×10(-8), the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8×10(-8)) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (?=8.74×10(-4), p=0.006).LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway.

SUBMITTER: Williams FM

PROVIDER: S-EPMC3686263 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.

Williams Frances M K FM Bansal Aruna T AT van Meurs Joyce B JB Bell Jordana T JT Meulenbelt Ingrid I Suri Pradeep P Rivadeneira Fernando F Sambrook Philip N PN Hofman Albert A Bierma-Zeinstra Sita S Menni Cristina C Kloppenburg Margreet M Slagboom P Eline PE Hunter David J DJ MacGregor Alex J AJ Uitterlinden Andre G AG Spector Tim D TD

Annals of the rheumatic diseases 20120919 7

<h4>Objective</h4>Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD.<h4>Methods</h4>We have developed a continuous trait based on disc space nar ...[more]

PMID: 22993228

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Project description:BackgroundAlthough it has been suggested that lumbar disc degeneration (LDD) is a significant risk factor for low back pain (LBP), its role remains uncertain. Our objective was to clarify the association between LDD and LBP and whether mental distress modifies the association.MethodsParticipants of a birth cohort underwent 1.5-T lumbar magnetic resonance imaging at the age of 47. The association between the sum score of LDD (Pfirrmann classification, range 0-15) and LBP (categorized into "no pain", "mild-to-moderate pain", "bothersome-and-frequent pain") was assessed using logistic regression analysis, with sex, smoking, body mass index, physical activity, occupational exposure, education, and presence of Modic changes and disc herniations as confounders. The modifying role of mental distress (according to the Hopkins Symptom Check List-25 [HSCL-25], the Beck Depression Inventory and the Generalized Anxiety Disorder Scale) in the association was analyzed using linear regression.ResultsOf the study population (n = 1505), 15.2% had bothersome and frequent LBP, and 29.0% had no LBP. A higher LDD sum score increased the odds of belonging to the "mild-to-moderate pain" category (adjusted OR corresponding to an increase of one point in the LDD sum score 1.11, 95% CI 1.04-1.18, P = 0.003) and the "bothersome-and-frequent pain" category (adjusted OR 1.20, 95% CI 1.10-1.31, P < 0.001), relative to the "no pain" category. Mental distress significantly modified the association between LDD and LBP, as a linear positive association was consistently observed among individuals without mental distress according to HSCL-25 (adjusted B 0.16, 95% CI 0.07-0.26, P < 0.001), but not among individuals with higher mental distress.ConclusionsLDD was significantly associated with both mild-to-moderate and bothersome-and-frequent LBP. However, the co-occurrence of mental distress diminished the association between LDD and LBP bothersomeness. Our results strongly suggest that mental symptoms affect the pain experience.

Dataset Information

Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.

Publications

Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.

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