BoneKEy Reports | BoneKEy Watch

A genetic basis for lower back pain?



DOI:10.1038/bonekey.2013.35

A genome-wide association study (GWAS) of 4683 individuals of European ancestry has identified four single nucleotide polymorphisms (SNPs) associated with lumbar disc degeneration (LDD), which involves narrowing of the disc space and osteophyte growth around the disc circumference, leading to lower-back pain. After developing a continuous trait based on disc-space narrowing and anterior and posterior osteophytes, the authors summed the subphenotypes over the five lumbar discs and used inverse normal transformation to approximate a normal distribution.

Of four SNPs that achieved genome-wide significance, three were on chromosome 6 and one on chromosome 3. The most significant SNP was within an intronic region of the PARK2 gene on chromosome 6; this gene encodes parkin, a component of a multiprotein E3 ubiquitin protein ligase complex. Differential methylation at the PARK2 promoter was observed in a small subset of subjects and was associated with LDD.

Two of the other SNPs were within an intron of PSMB9, a large multifunctional peptidase 2 gene within the class II region of the major histocompatibility complex. Falling slightly below genome-wide significance was an additional SNP within the MYH14 gene on chromosome 19; the gene encodes a non-muscle myosin.

Editor’s comment: This GWAS suggests novel variants in PARK2 and PSMB9, which may be involved in susceptibility to lower-back pain, a condition that is extremely common but not well understood.


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