The Genetic Epidemiology of Idiopathic Scoliosis

Overview

Journal Eur Spine J

Specialty Orthopedics

Date 2012 Jun 15

PMID 22695700

Citations 51

Authors

Kristen Fay Gorman

Cedric Julien

Alain Moreau

Affiliations

Soon will be listed here.

Abstract

Purpose: Idiopathic scoliosis is a complex developmental syndrome defined by an abnormal structural curvature of the spine. High treatment costs, chronic pain/discomfort, and the need for monitoring at-risk individuals contribute to the global healthcare burden of this musculoskeletal disease. Although many studies have endeavored to identify underlying genes, little progress has been made in understanding the etiopathogenesis. The objective of this comprehensive review was to summarize genetic associations/linkages with idiopathic scoliosis, as well as explore the strengths and weaknesses of each study, such that it may serve as a guide for the design and interpretation of future genetic studies in scoliosis.

Methods: We searched PubMed and Human Genome Epidemiology (HuGE) Navigator using the search terms "gene and scoliosis". Linkage or association studies published in English and available full-text were further analyzed as regards results, experimental design, and statistical approach.

Results: We identified and analyzed 50 studies matching our criteria. These consisted of 34 candidate gene studies (6 linkage, 28 association) and 16 genome-wide studies [14 pedigree-based linkage, 2 genome-wide association studies (GWAS)]. Findings involved genes related to connective tissue structure, bone formation/metabolism, melatonin signaling pathways, puberty and growth, and axon guidance pathways. Variability in results between studies suggested ethnic and/or genetic heterogeneity.

Conclusions: The major difficulty in idiopathic scoliosis research is phenotypic and genetic heterogeneity. Genetic research was overrepresented by underpowered studies. The use of biological endophenotypes, as well as restricted clinical definitions, may help to partition variation and increase the power of studies to detect or confirm an effect.

Citing Articles

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Genetic overlap between idiopathic scoliosis and schizophrenia in the general population.

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Assessment of the functional state of the back muscles in girls with C-shaped low-grade scoliosis in a tensiomyographic image: An observational cross-sectional study.

Szurmik T, Ogrodzka-Ciechanowicz K, Kurzeja P, Gasienica-Walczak B, Prusak J, Bibrowicz K PLoS One. 2023; 18(10):e0292555.

PMID: 37847728 PMC: 10581459. DOI: 10.1371/journal.pone.0292555.

References

McGregor T, Gurnett C, Dobbs M, Wise C, Morcuende J, Morgan T . Common polymorphisms in human lysyl oxidase genes are not associated with the adolescent idiopathic scoliosis phenotype. BMC Med Genet. 2011; 12:92. PMC: 3154146. DOI: 10.1186/1471-2350-12-92. View

Chen Z, Tang N, Cao X, Qiao D, Yi L, Cheng J . Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population. Eur J Hum Genet. 2008; 17(4):525-32. PMC: 2986210. DOI: 10.1038/ejhg.2008.203. View

Yeung H, Tang N, Lee K, Ng B, Hung V, Kwok R . Genetic association study of insulin-like growth factor-I (IGF-I) gene with curve severity and osteopenia in adolescent idiopathic scoliosis. Stud Health Technol Inform. 2006; 123:18-24. View

Esposito T, Uccello R, Caliendo R, Di Martino G, Gironi Carnevale U, Cuomo S . Estrogen receptor polymorphism, estrogen content and idiopathic scoliosis in human: a possible genetic linkage. J Steroid Biochem Mol Biol. 2009; 116(1-2):56-60. DOI: 10.1016/j.jsbmb.2009.04.010. View

Miller N, Marosy B, Justice C, Novak S, Tang E, Boyce P . Linkage analysis of genetic loci for kyphoscoliosis on chromosomes 5p13, 13q13.3, and 13q32. Am J Med Genet A. 2006; 140(10):1059-68. DOI: 10.1002/ajmg.a.31211. View

Suh K, Lee S, Hwang S, Kim S, Lee J . Elevated soluble receptor activator of nuclear factor-kappaB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J. 2007; 16(10):1563-9. PMC: 2078303. DOI: 10.1007/s00586-007-0390-2. View

Alden K, Marosy B, Nzegwu N, Justice C, Wilson A, Miller N . Idiopathic scoliosis: identification of candidate regions on chromosome 19p13. Spine (Phila Pa 1976). 2006; 31(16):1815-9. DOI: 10.1097/01.brs.0000227264.23603.dc. View

Qiu X, Tang N, Yeung H, Lee K, Hung V, Ng B . Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2007; 32(16):1748-53. DOI: 10.1097/BRS.0b013e3180b9f0ff. View

Morocz M, Czibula A, Grozer Z, Szecsenyi A, Almos P, Rasko I . Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2011; 36(2):E123-30. DOI: 10.1097/BRS.0b013e318a511b0e. View

10.

Nelson L, Ward K, Ogilvie J . Genetic variants in melatonin synthesis and signaling pathway are not associated with adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2010; 36(1):37-40. DOI: 10.1097/BRS.0b013e3181e8755b. View

11.

Weiss H . Idiopathic scoliosis: how much of a genetic disorder? Report of five pairs of monozygotic twins. Dev Neurorehabil. 2007; 10(1):67-73. DOI: 10.1080/13638490601005305. View

12.

Akoume M, Azeddine B, Turgeon I, Franco A, Labelle H, Poitras B . Cell-based screening test for idiopathic scoliosis using cellular dielectric spectroscopy. Spine (Phila Pa 1976). 2010; 35(13):E601-8. DOI: 10.1097/BRS.0b013e3181cf39ff. View

13.

Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N . Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004; 96(6):434-42. PMC: 7713993. DOI: 10.1093/jnci/djh075. View

14.

Peng Y, Liang G, Pei Y, Ye W, Liang A, Su P . Genomic polymorphisms of G-protein estrogen receptor 1 are associated with severity of adolescent idiopathic scoliosis. Int Orthop. 2011; 36(3):671-7. PMC: 3291774. DOI: 10.1007/s00264-011-1374-8. View

15.

Cheng J, Tang S, Guo X, Chan C, Qin L . Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine (Phila Pa 1976). 2001; 26(3):E19-23. DOI: 10.1097/00007632-200102010-00002. View

16.

Inoue M, Minami S, Nakata Y, Takaso M, Otsuka Y, Kitahara H . Prediction of curve progression in idiopathic scoliosis from gene polymorphic analysis. Stud Health Technol Inform. 2004; 91:90-6. View

17.

Xiao R, Boehnke M . Quantifying and correcting for the winner's curse in genetic association studies. Genet Epidemiol. 2009; 33(5):453-62. PMC: 2706290. DOI: 10.1002/gepi.20398. View

18.

Jiang J, Qian B, Mao S, Zhao Q, Qiu X, Liu Z . A promoter polymorphism of tissue inhibitor of metalloproteinase-2 gene is associated with severity of thoracic adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2011; 37(1):41-7. DOI: 10.1097/BRS.0b013e31820e71e3. View

19.

RISEBOROUGH E, WYNNE-DAVIES R . A genetic survey of idiopathic scoliosis in Boston, Massachusetts. J Bone Joint Surg Am. 1973; 55(5):974-82. View

20.

Varghese S . Matrix metalloproteinases and their inhibitors in bone: an overview of regulation and functions. Front Biosci. 2006; 11:2949-66. DOI: 10.2741/2024. View