Familial clustering and physiological risk factors associated with intervertebral disc degeneration in a large...

Our goals were to use a large medical genetics database to identify individuals that were diagnosed with intervertebral disc degeneration (IDD), determine whether IDD clusters in multigenerational families, define the magnitude of familial risk for IDD, and identify risk factors associated with IDD.

We searched the Utah Population Database to identify a cohort of patients diagnosed with IDD. Affected individuals were mapped to pedigrees to identify high-risk multigenerational families with excess clustering of IDD. Logistic regression models were used to calculate familial risk of IDD in related individuals. Physiological risk factors were evaluated using logistic regression models.

We identified 614 pedigrees with an excess clustering of IDD. The relative risk of developing IDD was significantly elevated in the first- and second-degree relatives of affected individuals. We identified a significant association of physiological risk factors with an IDD diagnosis, including unreported associations with epilepsy (OR = 1.64 [95% CI = 1.49-1.80]), cirrhosis/liver disease (OR = 1.84 [CI = 1.71-1.98]), and systemic lupus erythematosus (OR = 2.03 [95% CI = 1.31-3.16]). We discovered a potential new link between Gaucher Disease and IDD.

Familial clustering of IDD was observed in a large, statewide population. Our data indicate that genetic, physiological, and environmental factors may contribute to the disease process, further highlighting the complex and multifactorial nature of the disease.