title: Genetic association studies in lumbar disc degeneration: a systematic review.
abstract: 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.
authors.affiliation: Oulu Center for Cell - Matrix Research, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
authors.forename: Pasi J
authors.initials: PJ
authors.lastname: Eskola
authors.forename: Susanna
authors.initials: S
authors.lastname: Lemmelä
authors.forename: Per
authors.initials: P
authors.lastname: Kjaer
authors.forename: Svetlana
authors.initials: S
authors.lastname: Solovieva
authors.forename: Minna
authors.initials: M
authors.lastname: Männikkö
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.forename: Allan
authors.initials: A
authors.lastname: Lind-Thomsen
authors.forename: Kirsti
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
authors.forename: Kenneth M C
authors.initials: KM
authors.lastname: Cheung
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
authors.forename: Dino
authors.initials: D
authors.lastname: Samartzis
authors.forename: Jaro
authors.initials: J
authors.lastname: Karppinen
mesh_terms: D030541:Databases, Genetic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000235:genetics / Q000473:pathology; D017116:Low Back Pain / Q000473:pathology; D008279:Magnetic Resonance Imaging