Impact of Socioeconomic Status on the Risk of Intervertebral Disc Degeneration and Low Back Pain in the European Population and the Mediating Role of Obesity-Related Traits: Evidence from a Mendelian Randomization Study

Zhou Long,1 Qian Qin2 1Department of Neurosurgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of ChinaCorrespondence: Qian Qin, Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, People’s Republic of China, Email [email protected]: To identify the causal effect of socioeconomic status (SES) on intervertebral disc degeneration (IVDD) and low back pain risk through Mendelian Randomization (MR) analysis, and to evaluate the mediating role of obesity-related traits in these causal associations.Methods: Genome-wide association summary statistics for SESs ([i] years of schooling, [ii] occupational attainment, [iii] Townsend deprivation index, [iv] job involves heavy manual or physical work, and [v] average total household income before tax), obesity-related traits ([i] body mass index [BMI], [ii] waist circumference, and [iii] hip circumference), IVDD, and low back pain, were obtained from public databases. Inverse variance weighted (IVW) was the primary causal inference approach. Through two-step mediation MR analysis, key obesity-related traits mediating the causal effect of SES on the risk of IVDD and low back pain were identified.Results: This MR study supported that years of schooling reduced the risk of IVDD and low back pain, while the Townsend deprivation index and jobs involving heavy manual or physical work increased the risk of IVDD and low back pain. Additionally, occupational attainment and average total household income before tax reduced the risk of low back pain. Mediation MR analysis indicated that BMI and waist circumference mediated the causal effect of years of schooling, and BMI mediated the causal impact of average total household income before tax.Conclusions: This MR study provided evidence for the causal effect of genetically determined SES on the risk of IVDD and low back pain and revealed the potential mediating effect of obesity-related traits.Keywords: mediation mendelian randomization analysis, socioeconomic status, obesity, intervertebral disc degeneration, low back pain, causal inference