Showing papers by "Nancy L. Saccone published in 2023"

Evaluation of Genetic and Non-Genetic Risk Factors for Degenerative Cervical Myelopathy.

Abstract: STUDY DESIGN Cohort study. OBJECTIVE Our aim was to evaluate the associations of genetic and non-genetic factors with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA There is mounting evidence for an inherited predisposition for DCM, but uncertainty remains regarding specific genetic markers involved. Similarly, non-genetic factors are thought to play a role. MATERIALS AND METHODS Using diagnosis codes from hospital records linked to the UK Biobank cohort, patients with cervical spondylosis were identified followed by the identification of a subset with DCM. Non-genetic variables evaluated included age, sex, race, Townsend deprivation index, body mass index, occupational demands, osteoporosis and smoking. Genome-wide association analyses were conducted using logistic regression adjusted for age, sex, population principal components and follow-up. RESULTS 851 DCM cases out of 2787 cervical spondylosis patients were identified. Several non-genetic factors were independently associated with DCM including age (odds ratio [OR]=1.11, 95%CI=1.01-1.21, P=0.024), male sex (OR =1.63, 95%CI=1.37-1.93, P<0.001) and relative socioeconomic deprivation (OR=1.03, 95%CI=1.00-1.06, P=0.030). Asian race was associated with lower DCM risk (OR=0.44, 95%CI=0.22-0.85, P=0.014). We did not identify genome-wide significant (≤5×10-8) single nucleotide polymorphisms (SNPs) associated with DCM. The strongest genome-wide signals were at SNP rs67256809 in the intergenic region of the genes LINC02582 and FBXO15 on chromosome 18 (P=1.12×10-7) and rs577081672 in the GTPBP1 gene on chromosome 22 (P=2.9×10-7). No SNPs reported in prior DCM studies were significant after adjusting for replication attempts. CONCLUSION Increasing age, male sex and relative socioeconomic deprivation were identified as independent risk factors for DCM, whereas Asian race was inversely associated. SNPs of potential interest were identified in GTPBP1 and an intergenic region on chromosome 18, but these associations did not reach genome-wide significance. Identification of genetic and non-genetic DCM susceptibility markers may guide understanding of DCM disease processes, inform risk, guide prevention and potentially inform surgical outcomes. LEVEL OF EVIDENCE Prognostic Level III. See instructions for Authors for complete description of levels of evidence.