title: Two subtypes of intervertebral disc degeneration distinguished by large-scale population-based study.
abstract: Lumbar disc degeneration (LDD) is a major cause of low back pain, and is a common and disabling condition worldwide. It has been defined and measured by multiple spine magnetic resonance imaging (MRI) features, but the heterogeneity among them has never been fully addressed.
  
  
  
  This study examined the intercorrelations, risk factor associations, and single nucleotide polymorphism (SNP) heritabilities of lumbar disc MRI features in a large-scale sample to classify the different intervertebral disc phenotypes associated with LDD.
  
  
  
  A cross-sectional study was conducted consisting of 2,943 volunteers of Southern Chinese origin (mean age: 41.1 years; range: 15-55 years; 59.6% women).
  
  
  
  The outcome measures were MRI phenotypic spinal patterns and their risk factor profiles in relation to developmental or degenerative origins of disc degeneration.
  
  
  
  Sagittal T2-weighted MRI of the lumbar spine from L1 to S1 was assessed. The MRI features of lumbar intervertebral disc changes, such as disc signal intensity loss and disc bulges or extrusions, as well as additional imaging phenotypes of end plate changes, high-intensity zones, and bone marrow changes, were evaluated. Blood samples were taken for genotyping using the HumanOmni-ZhongHua-8 BeadChip. Subject demographics, environmental, and lifestyle factors were assessed by questionnaires. Multivariate statistical techniques were used for phenotype evaluation. Polychoric correlations and local regression statistical analyses were performed. The genetic components contributed by common SNPs were estimated by comparing genetic correlations and phenotypic correlations using the Genome-Wide Complex Trait Analysis (GCTA) tool.
  
  
  
  The study noted that lumbar disc MRI features separated into two groups with differential patterns of risk factor associations. A subset of lumbar disc abnormalities, including end plate changes but also upper lumbar disc bulging and signal intensity loss, may have a developmental origin. Subsequent degenerative changes, typically affecting the lower lumbar discs, then emerge as individuals age and are associated with body mass index.
  
  
  
  This is the first large-scale study to identify two distinct patterns of lumbar disc alterations, noting degenerative changes and a possible developmental component affecting the lumbar spine. This new classification provides a starting point for a more homogeneous phenotype definition, which may provide greater statistical power and precision in future genetic and epidemiologic studies. In addition, such insights may have direct clinical implications in the prevention, therapeutics, and prognostics of patients with disc degeneration.
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, 5 Sassoon Rd, Pokfulam, Hong Kong SAR, China; Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China.
authors.forename: Dino
authors.initials: D
authors.lastname: Samartzis
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, 5 Sassoon Rd, Pokfulam, Hong Kong SAR, China; Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Desmond D
authors.initials: DD
authors.lastname: Campbell
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, 5 Sassoon Rd, Pokfulam, Hong Kong SAR, China; Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China.
authors.forename: Kenneth M C
authors.initials: KM
authors.lastname: Cheung
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China.
authors.forename: Keith D K
authors.initials: KD
authors.lastname: Luk
authors.affiliation: Medical Research Center Oulu, University of Oulu, Pentti Kaiteran katu 190570, Oulu, Finland; Oulu University Hospital, Center for Life Course Health Research, University of Oulu, Pentti Kaiteran katu 190570, Oulu, Finland; Finnish Institute of Occupational Health, Pentti Kaiteran katu 190570, Oulu, Finland.
authors.forename: Jaro
authors.initials: J
authors.lastname: Karppinen
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Cheah
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, 5 Sassoon Rd, Pokfulam, Hong Kong SAR, China; Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China. Electronic address: pcsham@hku.hk.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000145:classification / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012907:Smoking
keywords: Degeneration; Development; Disc; Genetics; Intervertebral; Lumbar; MRI; Risk factors