intervertebral disc degeneration, model

Intervertebral Disc Degeneration with Atherosclerosis

Degenerative Disc Model

Atherosclerosis is a chronic inflammatory cardiovascular disease in which a dysfunction of the arterial wall leads to the formation of plaque or even other cardiovascular diseases. Cardiovascular diseases like this have high mortality rates because they lead to other cardiovascular diseases like heart attacks and stroke, and even non-cardiovascular diseases like intervertebral disc degeneration.

Intervertebral disc degeneration is a common condition that is prevalent with increased age and is characterized by a dysfunctional intervertebral disc. Much more than genetics, environmental and lifestyle factors play key roles in the occurrence of the disease. However, this research summary gives an overview of the study which used genetic variants of atherosclerosis as proxies for exposure to establish whether the exposure is contributively related to Intervertebral Disc Degeneration (IDD). The study1 aimed to ease the development of therapeutic mediation for these diseases.

Research Process and Data Analyses

Mendelian randomization was the statistical tool used to determine causality. This study did not involve human subjects or personal information, as researchers used summary statistics from two Genome-Wide Association Studies(GWAS). The first and second GWAS summarized statistics for genetic variants associated with atherosclerosis and IDD, respectively. All the cases reported in both GWAS were of people of European ancestry.

Imaging techniques like coronary angiography, carotid ultrasound, and computed tomography angiography were used to assess atherosclerosis. In contrast, standardized clinical assessments, radiographic imaging (such as MRI and CT scans), and patient-reported outcomes were used to assess IDD. 

A two-sample approach was employed. Genetic variants associated with atherosclerosis were identified and selected in the first sample and then tested against the second sample to determine their association with IDD.

The following criteria were maintained for genetic variants

  1. Genetic variants were independent of each other
  2. They were ensured to have genome-wide significance
  3. They had no association with known confounders of the IDD-atherosclerosis relationship
  4. The genetic variants from the first GWAS dataset had to be present in the second GWAS dataset


Results a
nd Findings

After statistical analyses with the R statistical software, 31 genetic variants associated with atherosclerosis from the first GWAS dataset met the inclusion criteria and were used in the second GWAS dataset as instrumental variables to test and gauge the effect of atherosclerosis on IDD. Upon completion of the MR analysis, sufficient evidence for a causal link between atherosclerosis and IDD was established.

This means that therapeutic developments and interventions, such as lifestyle modifications and pharmacological treatments, that can possibly remediate atherosclerosis may have huge benefits, reducing the risk of IDD in IDD-predisposed patients. This study plugged the knowledge gap, improving on the foundation of other observational studies by establishing causal evidence using an unbiased and objective approach. The study also highlighted the strength of using summary statistics from large-scale GWAS datasets.

Further studies need to be carried out to understand better the pathophysiological mechanisms that these two conditions share. This will help us fully understand the best therapeutic strategy for remediating both conditions.

Limitations of the Study

  1. The datasets used in this study were based on European ancestry only, so this study doesn’t consider the genetic variants associated with both atherosclerosis and IDD that may be present in other populations.
  2. Also, this study only explored the causal association between Atherosclerosis and IDD. However, other factors besides Atherosclerosis may significantly contribute to the occurrence of IDD.
  3. This study does not provide further knowledge on the biological mechanisms and pathways that connect genetic variants to exposure to atherosclerosis and the outcome of IDD, and this limited knowledge may significantly affect the results presented in this study.


Having established significant evidence for a causal association between atherosclerosis and IDD using the unbiased Mendelian Randomization method, thereby highlighting the strength of the statistical method, researchers and scientists can confidently take further steps in understanding the underlying mechanisms and pathways which connect genetic variants that are associated with atherosclerosis to IDD, leading to the development of therapeutic methods with which to treat atherosclerosis and remediate Intervertebral Disc Degeneration.