Skip to main content
Article thumbnail
Location of Repository

Understanding Genetic Factors in Idiopathic Scoliosis, a Complex Disease of Childhood

By Carol A Wise, Xiaochong Gao, Scott Shoemaker, Derek Gordon and John A Herring

Abstract

Idiopathic scoliosis (AIS) is the most common pediatric spinal deformity, affecting ~3% of children worldwide. AIS significantly impacts national health in the U. S. alone, creating disfigurement and disability for over 10% of patients and costing billions of dollars annually for treatment. Despite many investigations, the underlying etiology of IS is poorly understood. Twin studies and observations of familial aggregation reveal significant genetic contributions to IS. Several features of the disease including potentially strong genetic effects, the early onset of disease, and standardized diagnostic criteria make IS ideal for genomic approaches to finding risk factors. Here we comprehensively review the genetic contributions to IS and compare those findings to other well-described complex diseases such as Crohn’s disease, type 1 diabetes, psoriasis, and rheumatoid arthritis. We also summarize candidate gene studies and evaluate them in the context of possible disease aetiology. Finally, we provide study designs that apply emerging genomic technologies to this disease. Existing genetic data provide testable hypotheses regarding IS etiology, and also provide proof of principle for applying high-density genome-wide methods to finding susceptibility genes and disease modifiers

Topics: Article
Publisher: Bentham Science Publishers Ltd.
OAI identifier: oai:pubmedcentral.nih.gov:2674301
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2007). A common allele on chromosome 9 associated with coronary heart disease. Science
    2. (2001). A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature
    3. (2002). A genetic locus for adolescent idiopathic scoliosis linked to chromosome 19p13.3.
    4. (1973). A genetic survey of idiopathic scoliosis in
    5. (2006). A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science
    6. (2001). A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases.
    7. (2003). A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis.
    8. (2006). A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases. Spine
    9. (2007). A unified genetic theory for sporadic and inherited autism.
    10. (2007). Adolescent idiopathic scoliosis in twins: a population-based survey. Spine
    11. (1994). Adolescent idiopathic scoliosis. Lancet
    12. (1987). American Academy of Orthopaedic Surgeons. Position Statement, School Screening Programs for the Early Detection of Scoliosis. Park Ridge, IL, American Academy of Orthopaedic Surgeons,
    13. (1993). An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine
    14. (2001). Analyzing developmental trajectories of distinct but related behaviors: a group-based method.
    15. (1999). Analyzing developmental trajectories: a semi-parametric, group-based approach.
    16. (2008). Applied Survival Analysis: Regression Modeling of Time to Event Data. in:
    17. (2005). Array comparative genomic hybridization and its applications in
    18. (2002). Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11.
    19. (2006). Association of estrogen receptor gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine
    20. (2005). Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls.
    21. (1995). Autosomal dominant idiopathic scoliosis?
    22. (2007). CHD7 gene polymorphisms are associated with susceptibility to idiopathic scoliosis.
    23. (1997). Clinical and electrophysiological phenotype of a homozygously duplicated CharcotMarie-Tooth (type 1A) disease.
    24. (2005). Clinical features of 78 adults with 22q11 deletion syndrome.
    25. (2002). Common skeletal deformities. In: Rimoin DL,
    26. (2005). Complement factor H polymorphism and agerelated macular degeneration. Science
    27. (2005). Complement factor H polymorphism in age-related macular degeneration. Science
    28. (2005). Complement factor H variant increases the risk of age-related macular degeneration. Science
    29. Detection of large-scale variation in the human genome.
    30. (2003). Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease.
    31. (1922). Eine skoliotikerfamilie. Ein Beitrag zur Frage der kongenitalen Skoliose und der Hereditat
    32. Etiology of idiopathic scoliosis: current trends in research.
    33. (2005). Factors affecting statistical power in the detection of genetic association.
    34. (2003). Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus. Spine
    35. (1991). Familial occurrence of inflammatory bowel
    36. (1996). Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis.
    37. (1995). Genetic analysis of type 1 diabetes using whole genome approaches.
    38. (1970). Genetic aspects of idiopathic scoliosis. A Nicholas Andry Award essay,
    39. (2003). Genetic power calculator: design of linkage and association genetic mapping studies of complex traits.
    40. (1971). Genetic studies in scoliosis.
    41. (2005). Identification of candidate regions for familial idiopathic scoliosis. Spine
    42. (1997). Idiopathic scoliosis-new surgical methods or search for the reasons. Acta Chirurgica Hungarica
    43. Idiopathic scoliosis, genetic and environmental aspects.
    44. (2006). Idiopathic scoliosis: identification of candidate regions on chromosome 19p13. Spine
    45. (2002). In: Tachdjian’s Pediatric Orthopaedics.
    46. (1975). Infantile idiopathic scoliosis. Causative factors, particularly in the first six months of life.
    47. (2006). Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies.
    48. (2004). Large-scale copy number polymorphism in the human genome. Science
    49. (2005). Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin
    50. (2000). Localization of susceptibility to familial idiopathic scoliosis. Spine
    51. (1991). Lung function in adult idiopathic scoliosis: a 20 year follow up. Thorax
    52. (2004). Mapping complex disease loci in whole-genome association studies. Nature
    53. (2007). Melatonin receptor 1B (MBTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine
    54. (2004). Melatonin signaling dysfunction in adolescent idiopathic scoliosis. Spine
    55. (1996). Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2).
    56. (2004). Mutations in a human ROBO3 gene disrupt hindbrain axon pathway crossing and morphogenesis. Science
    57. (2007). NCI-NHGRI Working Group on Replication in Association Studies. Replicating genotype-phenotype associations. Nature
    58. (2008). Next-generation sequencing transforms today's biology.
    59. (2005). Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis.
    60. (1999). Pathogenesis of idiopathic scoliosis. Spine
    61. (2006). Persistent osteopenia in adolescent idiopathic scoliosis--longitudinal monitoring of bone mineral density until skeletal maturity.
    62. (1999). Persistent osteopenia in adolescent idiopathic scoliosis. A longitudinal follow up study. Spine
    63. (2001). Pineal transplantation after pinealectomy in young chickens has no effect on the development of scoliosis. Spine
    64. (2004). Pinealectormy induces malformations of the spine and reduces the mechanical strength of the vertebrae in Atlantic salmon, Salmo
    65. (1981). Prader-Willi syndrome and scoliosis.
    66. (1989). Precise localization of NF1 to 17q11.2 by balanced translocation.
    67. Progression of the curve in boys who have idiopathic scoliosis.
    68. (2007). QuantiSNP: an objective Bayes Hidden-Markov model to detect and accurately map copy number variation using SNP genotyping data. Nuc. Acids Res.
    69. (1997). Role of serotonin for scoliotic deformity in pinealectomized chicken. Spine
    70. (1997). Scoliosis in twins. A meta-analysis of the literature and report of six cases. Spine
    71. (1978). Scoliosis: incidence and natural history. A prospective epidemiological study.
    72. (2000). Searching for genetic determinants in the new millennium.
    73. (1992). Segregation of structural collagen genes in adolescent idiopathic scoliosis.
    74. (2006). Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1
    75. (2008). Sequence census methods for functional genomics.
    76. (2004). SNTG1, the gene encoding gamma1-syntrophin: a candidate gene for idiopathic scoliosis.
    77. (2007). Spine deformity in spinal muscular atrophy.
    78. (2007). Strong association of de novo copy number changes in autism. Science
    79. (1998). The genetics of psoriasis: a complex disorder of the skin and immune system.
    80. (1994). The potential role of the elastic fiber system in adolescent idiopathic scoliosis.
    81. (2006). The search for idiopathic scoliosis genes. Spine
    82. (2006). Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.