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dc.contributor.authorWilliams, Frances M K
dc.contributor.authorBansal, Aruna T
dc.contributor.authorvan Meurs, Joyce B
dc.contributor.authorBell, Jordana T
dc.contributor.authorMeulenbelt, Ingrid
dc.contributor.authorSuri, Pradeep
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorSambrook, Philip N
dc.contributor.authorHofman, Albert
dc.contributor.authorBierm-Zeinstra, Sita
dc.contributor.authorMenni, Cristina
dc.contributor.authorKloppenburg, Megreet
dc.contributor.authorSlagboom, P Eline
dc.contributor.authorHunter, David J.
dc.contributor.authorMacGregor, Alex J
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorSpector, Tim D
dc.date.accessioned2014-01-31T04:47:54Z
dc.date.available2014-01-31T04:47:54Z
dc.date.issued2013-07
dc.identifier.citationAnn Rheum Dis. 2013 Jul;72(7):1141-8.en_AU
dc.identifier.issn1468-2060
dc.identifier.urihttp://hdl.handle.net/2123/9966
dc.description.abstractOBJECTIVE: 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. METHODS: 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. RESULTS: This study of 4600 individuals identified four single nucleotide polymorphisms with p<5x10(-8), the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8x10(-8)) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (beta=8.74x10(-4), p=0.006). CONCLUSIONS: 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.en_AU
dc.language.isoenen_AU
dc.publisherBMJen_AU
dc.relationK12HD01097 (United States NICHD NIH HHS), N01-HC-25195 (United States NHLBI NIH HHS)en_AU
dc.subjectGene polymorphismen_AU
dc.subjectlow back painen_AU
dc.subjectMRIen_AU
dc.titleNovel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.en_AU
dc.typeArticleen_AU
dc.subject.asrcFoR::110322 - Rheumatology and Arthritisen_AU
dc.identifier.doidoi: 10.1136/annrheumdis-2012-201551
dc.type.pubtypePre-printen_AU


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