Skip to main content
Top
Published in: Current Osteoporosis Reports 1/2023

21-01-2023 | Back Pain | Genetics (D Karasik and C Ackert-Bicknell, Section Editors)

Genetics of Intervertebral Disc Degeneration

Authors: David C. Ou-Yang, Christopher J. Kleck, Cheryl L. Ackert-Bicknell

Published in: Current Osteoporosis Reports | Issue 1/2023

Login to get access

Abstract

Purpose of Review

Intervertebral disc degeneration is a contributor to chronic back pain. While a part of the natural aging process, early or rapid intervertebral disc degeneration is highly heritable. In this review, we summarize recent progress towards unraveling the genetics associated with this degenerative process.

Recent Findings

Use of large cohorts of patient data to conduct genome-wide association studies (GWAS) for intervertebral disc disease, and to lesser extent for aspects of this process, such as disc height, has resulted in a large increase in our understanding of the genetic etiology. Genetic correlation suggests that intervertebral disc disease is pleiotropic with risk factors for other diseases such as osteoporosis. The use of Mendelian Randomization is slowly establishing what are the causal relationships between intervertebral disc disease and factors previously correlated with this disease.

Summary

The results from these human genetic studies highlight the complex nature of this disease and have the potential to lead to improved clinical management of intervertebral disc disease. Much additional work should now be focused on characterizing the causative relationship various co-morbid conditions have with intervertebral disc degeneration and on finding interventions to slow or halt this disease.
Literature
5.
go back to reference Torgerson WR, Dotter WE. Comparative roentgenographic study of the asymptomatic and symptomatic lumbar spine. J Bone Joint Surg Am. 1976;58(6):850–3.CrossRefPubMed Torgerson WR, Dotter WE. Comparative roentgenographic study of the asymptomatic and symptomatic lumbar spine. J Bone Joint Surg Am. 1976;58(6):850–3.CrossRefPubMed
9.
go back to reference Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K. 1995 Volvo Award in clinical sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine (Phila Pa 1976). 1995;20(24):2601–12.CrossRefPubMed Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K. 1995 Volvo Award in clinical sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine (Phila Pa 1976). 1995;20(24):2601–12.CrossRefPubMed
10.
go back to reference • Trefilova VV, Shnayder NA, Petrova MM, Kaskaeva DS, Tutynina OV, Petrov KV, et al. The Role of Polymorphisms in Collagen-Encoding Genes in Intervertebral Disc Degeneration. Biomolecules. 2021;11(9) https://doi.org/10.3390/biom11091279. This paper is a comprehensive exploration of polymorphisms in structural collagen genes to test for association with disc degeneration. This study provides an excellent overview of the role of matrix structural gene contribution to the genetic etiology of disc degeneration. • Trefilova VV, Shnayder NA, Petrova MM, Kaskaeva DS, Tutynina OV, Petrov KV, et al. The Role of Polymorphisms in Collagen-Encoding Genes in Intervertebral Disc Degeneration. Biomolecules. 2021;11(9) https://​doi.​org/​10.​3390/​biom11091279. This paper is a comprehensive exploration of polymorphisms in structural collagen genes to test for association with disc degeneration. This study provides an excellent overview of the role of matrix structural gene contribution to the genetic etiology of disc degeneration.
12.
go back to reference • Cherif H, Mannarino M, Pacis AS, Ragoussis J, Rabau O, Ouellet JA, et al. Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration. Int J Mol Sci. 2022;23(7) https://doi.org/10.3390/ijms23073993. In this study, the authors explored gene expression changes in the degenerating disc. They identify several pathways perturbated by this disease state. • Cherif H, Mannarino M, Pacis AS, Ragoussis J, Rabau O, Ouellet JA, et al. Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration. Int J Mol Sci. 2022;23(7) https://​doi.​org/​10.​3390/​ijms23073993. In this study, the authors explored gene expression changes in the degenerating disc. They identify several pathways perturbated by this disease state.
30.
go back to reference Nathan M, Pope MH, Grobler LJ. Osteophyte formation in the vertebral column: a review of the etiologic factors--Part II. Contemp Orthop. 1994;29(2):113–9.PubMed Nathan M, Pope MH, Grobler LJ. Osteophyte formation in the vertebral column: a review of the etiologic factors--Part II. Contemp Orthop. 1994;29(2):113–9.PubMed
33.
go back to reference Varlotta GP, Brown MD, Kelsey JL, Golden AL. Familial predisposition for herniation of a lumbar disc in patients who are less than twenty-one years old. J Bone Joint Surg Am. 1991;73(1):124–8.CrossRefPubMed Varlotta GP, Brown MD, Kelsey JL, Golden AL. Familial predisposition for herniation of a lumbar disc in patients who are less than twenty-one years old. J Bone Joint Surg Am. 1991;73(1):124–8.CrossRefPubMed
46.
go back to reference Jones G, Nguyen T, Sambrook PN, Kelly PJ, Eisman JA. A longitudinal study of the effect of spinal degenerative disease on bone density in the elderly. J Rheumatol. 1995;22(5):932–6.PubMed Jones G, Nguyen T, Sambrook PN, Kelly PJ, Eisman JA. A longitudinal study of the effect of spinal degenerative disease on bone density in the elderly. J Rheumatol. 1995;22(5):932–6.PubMed
57.
go back to reference •• Bjornsdottir G, Stefansdottir L, Thorleifsson G, Sulem P, Norland K, Ferkingstad E, et al. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology. Nat Commun. 2022;13(1):634. https://doi.org/10.1038/s41467-022-28167-1. This is the largest genome wide association study conducted todate for IVD. It is conducted in concert with dorsalgia/back pain and provides an unbiased examination of the genetic interplay between these two conditions. •• Bjornsdottir G, Stefansdottir L, Thorleifsson G, Sulem P, Norland K, Ferkingstad E, et al. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology. Nat Commun. 2022;13(1):634. https://​doi.​org/​10.​1038/​s41467-022-28167-1. This is the largest genome wide association study conducted todate for IVD. It is conducted in concert with dorsalgia/back pain and provides an unbiased examination of the genetic interplay between these two conditions.
63.
go back to reference Suri P, Palmer MR, Tsepilov YA, Freidin MB, Boer CG, Yau MS, Evans DS, Gelemanovic A, Bartz TM, Nethander M, Arbeeva L, Karssen L, Neogi T, Campbell A, Mellstrom D, Ohlsson C, Marshall LM, Orwoll E, Uitterlinden A, et al. Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. PLoS Genet. 2018;14(9):e1007601. https://doi.org/10.1371/journal.pgen.1007601. Suri P, Palmer MR, Tsepilov YA, Freidin MB, Boer CG, Yau MS, Evans DS, Gelemanovic A, Bartz TM, Nethander M, Arbeeva L, Karssen L, Neogi T, Campbell A, Mellstrom D, Ohlsson C, Marshall LM, Orwoll E, Uitterlinden A, et al. Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. PLoS Genet. 2018;14(9):e1007601. https://​doi.​org/​10.​1371/​journal.​pgen.​1007601.
Metadata
Title
Genetics of Intervertebral Disc Degeneration
Authors
David C. Ou-Yang
Christopher J. Kleck
Cheryl L. Ackert-Bicknell
Publication date
21-01-2023
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 1/2023
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-022-00769-0

Other articles of this Issue 1/2023

Current Osteoporosis Reports 1/2023 Go to the issue

Nutrition, Exercise and Lifestyle (S Shapses and R Daly, Section Editors)

Energy Balance and Bone Health: a Nutrient Availability Perspective

Bone Marrow and Adipose Tissue (B Lecka-Czernik and G Duque, Section Editors)

Update on the Role of Glucocorticoid Signaling in Osteoblasts and Bone Marrow Adipocytes During Aging

Therapeutics and Medical Management (S Jan De Beur and B Clarke, Section Editors)

Denosumab Discontinuation

Bone and Diabetes (A Schwartz and P Vestergaard, Section Editors)

The Gut-Bone Axis in Diabetes