Identification of a Novel Genetic Variant Associated with Adjacent Segment Disease: Analysis of Spinal Fusions in the UK BioBank

Introduction: The prevalence of symptomatic spinal disease requiring fusion is increasing with an aging population. Patients are informed of a 3% annual risk of additional surgery due to adjacent segment disease (AdSD) without accounting for advances in surgical technique. The UK BioBank (UKB) is a population-based cohort of 500,000 deidentified people, with genetic and non-genetic information, as well as hospital records. The database is regularly updated and includes >20 years of hospital records. We aim to investigate the rate of AdSD after primary cervical and lumbar fusion in the UKB cohort, as well as risk factors that may contribute.

Methods: UKB patients that underwent primary lumbar or cervical fusion, as well as ACF or PCF were identified using OPCS-4 codes. AdSD was the endpoint, defined as subsequent fusion, revision, or decompression. Risk factors were assessed using multivariable Cox regression analysis. Cumulative incidence was calculated to estimate the annual risk of AdSD. GWAS analysis was performed to identify small nucleotide polymorphisms (SNPs) associated with AdSD.

Results: 3487 patients underwent primary fusion in the cervical (N=1732, ACF = 1571, PCF = 121, combined = 42) or lumbar (N=1755) spine. 211 (12.1%) cervical and 230 (13.1%) lumbar patients were revised for AdSD. 5-year AdSD rate was 8.33% (cervical) and 10.24% (lumbar), and at 20-years was 20% (cervical) and 19.84% (lumbar), amounting to an annual risk of ~1%. Unemployed/retired status achieved significance as a risk factor for all AdSD patients (p=0.0063). GWAS analysis for all AdSD patients identified a novel SNP (rs116459848, Chromosome 5). Previously reported SNPs associated with degenerative pathologies failed to achieve significance.

Conclusion : The combined risk of AdSD for lumbar and cervical spine fusion is lower than previously reported, 1% annually with about 40% of cases occurring within the first 5 years and remaining cases occurring in the following 15 years. There may be risk factors accounting for increased early rate of AdSD, including surgical factors and patient factors. We identified a novel SNP that associated with AdSD cases in the absence of SNPs associated with degenerative pathologies. This suggests there may be a novel genetic component to AdSD, and AdSD may represent a separate disease.