Abstract
Back pain (BP) is a common condition of major social importance and poorly understood pathogenesis. Intervertebral lumbar disc degeneration in all its guises is one of the major biological risk factors for BP. Previously, we identified the locus at 8q24.21 associated with chronic BP, which has been found elsewhere associated with sciatica after surgery for lumbar disc herniation. In the current study we used co-localisation methods to identify the gene most likely to harbor the causal variant. We show that the same functional variant at the 8q24.21 locus is responsible for both lumbar disc degeneration and BP, and we also studied the effects of this locus on related phenotypes. Our results link the locus to intervertebral disc and bone mineral density, but not to anthropometric measurements, thus corroborating the epidemiological evidence. Moreover, the same functional variant at the locus is more likely to affect the expression of the nearby FAM49B gene, rather than the GSDMC gene, which was previously proposed as a causative one for BP.
Highlights
Back pain (BP) is a common debilitating condition with a lifetime prevalence of 40% and a major socioeconomic impact[1]
Cases were defined as those having BP of duration >3-6 months; controls included those without back pain or with back pain of
The location chr8:130,717,716 is tagged by intergenic variant rs10956487 which is in perfect LD with rs6651255 (r2=1 according to 1000 Genomes EUR samples), the lead SNP in the Icelandic study of lumbar disc herniation (LDH) by Bjornsdottir et al.[19]
Summary
Back pain (BP) is a common debilitating condition with a lifetime prevalence of 40% and a major socioeconomic impact[1]. Rather than a discrete disease, LDD is considered a continuous lifelong aging process that usually starts in the third decade of life but may be seen in children[4]. It is highly heritable[5], as well as being influenced by smoking[6], age[7] and body mass index[8]. There is a clear genetic predisposition to both BP and LDD with estimates of heritability in the range of 30%–70%12–15 These traits have been shown to share genetic risk factors[16]. Little is known about the genetic architecture of BP and only three associated genetic loci have been identified[17,18]
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