Genetic association studies in lumbar disc degeneration: a systematic review

PLoS One. 2012;7(11):e49995. doi: 10.1371/journal.pone.0049995. Epub 2012 Nov 21.


Objective: Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans.

Methods: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines.

Results: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328) and MMP9 (rs17576).

Conclusions: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Databases, Genetic*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Humans
  • Intervertebral Disc Degeneration* / genetics
  • Intervertebral Disc Degeneration* / pathology
  • Intervertebral Disc Displacement* / genetics
  • Intervertebral Disc Displacement* / pathology
  • Low Back Pain / pathology
  • Magnetic Resonance Imaging

Supplementary concepts

  • Intervertebral disc disease

Grants and funding

This study was supported in part by grants from the Academy of Finland (grants 121620 and 129504, to JK). The Päivikki and Sakari Sohlberg Foundation, the Eemil Aaltonen Foundation, the Finnish-Norwegian Medical Foundation and the Finnish Medical Foundation have supported PE. SL was financially supported by the Academy of Finland (MSDs@Lifecourse Concortium, Responding to Public Health Challenges (SALVE), project no 129364). PK was supported by a grant from the Danish Agency for Science, Technology and Innovation (271-08-0374). This work was further supported by an Area of Excellence grant from the University Grants Committee of Hong Kong (AoE/M-04/04). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.