Genetics and Functional Pathology of Idiopathic Scoliosis

  • Elizabeth A. Terhune
  • Erin E. Baschal
  • Nancy Hadley MillerEmail author


Idiopathic scoliosis (IS) has been understood to have a familial or genetic component for decades, yet the genetic mechanisms underlying the disorder are still a subject of active investigation. Identification of genes related to this condition has been difficult due to a number of factors, including genetic heterogeneity, phenotypic heterogeneity, and inconsistent exclusion and inclusion criteria for genetic study participants. Discoveries have kept pace with available genetic technologies, with potentially causal genes and regions having been identified by linkage analyses, candidate gene sequencing, genome-wide association studies (GWAS), and next-generation sequencing methods. The genetic associations with IS that have been replicated to date are variants in or near LBX1 and GPR126, as well as rare variants in multiple extracellular matrix genes. Early animal models of IS have included pinealectomized chickens and bipedal rodents, which led to an interest in melatonin signaling dysfunction as a possible cause of IS. Bony fishes have recently emerged as leading models of IS, starting with the curveback mutant guppy line and progressing to the zebrafish, which was more recently used to create a late-onset scoliosis phenotype through mutations in ptk7 and other motile cilia genes. Today, these animal models in combination with modern sequencing technologies provide powerful tools for the IS research community, with immense potential toward the discovery of additional IS candidate genes and pathways. Determining the genetic factors underlying IS may ultimately improve patient care through diagnostic testing and treatments for affected children.


Genetics Complex traits Idiopathic scoliosis Animal models Candidate genes Genetic variants 



We thank the laboratory of Dr. Brian Ciruna for providing the micro-CT image of the mutant ptk7 zebrafish in Fig. 7.2.


  1. 1.
    Garland HG. Hereditary scoliosis. Br Med J. 1934;1:328.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wynne-Davies R. Familial (idiopathic) scoliosis. A family survey. J Bone Joint Surg Br. 1968;50(1):24–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Faber A. Untersuchungen uber die Erblichkeit der Skoliose. Arch Orthop Unfallchir. 1936;36:247–9.Google Scholar
  4. 4.
    Ma XJ, Hu P. The etiological study of idiopathic scoliosis. Zhonghua Wai Ke Za Zhi. 1994;32(8):504–6.PubMedGoogle Scholar
  5. 5.
    MacEwen GD, Shands AR Jr. Scoliosis--a deforming childhood problem. Clin Pediatr (Phila). 1967;6(4):210–6.CrossRefGoogle Scholar
  6. 6.
    Perricone G, Paradiso T. Familial factors in so-called idiopathic scoliosis. Chir Organi Mov. 1987;72(4):355–8.PubMedGoogle Scholar
  7. 7.
    De George FV, Fisher RL. Idiopathic scoliosis: genetic and environmental aspects. J Med Genet. 1967;4(4):251–7.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Riseborough EJ, Wynne-Davies R. A genetic survey of idiopathic scoliosis in Boston, Massachusetts. J Bone Joint Surg Am. 1973;55(5):974–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Bonaiti C, Feingold J, Briard ML, Lapeyre F, Rigault P, Guivarch J. Genetics of idiopathic scoliosis. Helv Paediatr Acta. 1976;31(3):229–40.PubMedGoogle Scholar
  10. 10.
    Ogilvie JW, Braun J, Argyle V, Nelson L, Meade M, Ward K. The search for idiopathic scoliosis genes. Spine. 2006;31(6):679–81.CrossRefPubMedGoogle Scholar
  11. 11.
    Carr AJ. Adolescent idiopathic scoliosis in identical twins. J Bone Joint Surg Br. 1990;72(6:1077.CrossRefGoogle Scholar
  12. 12.
    Gaertner RL. Idiopathic scoliosis in identical (monozygotic) twins. South Med J. 1979;72(2):231–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Senda M, Harada Y, Nakahara S, Inoue H. Lumbar spinal changes over 20 years after posterior fusion for idiopathic scoliosis. Acta Med Okayama. 1997;51(6):327–31.PubMedGoogle Scholar
  14. 14.
    Kesling KL, Reinker KA. Scoliosis in twins. A meta-analysis of the literature and report of six cases. Spine. 1997;22(17):2009–14. discussion 15CrossRefPubMedGoogle Scholar
  15. 15.
    McKinley LM, Leatherman KD. Idiopathic and congenital scoliosis in twins. Spine. 1978;3(3):227–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Murdoch G. Scoliosis in twins. J Bone Joint Surg Br. 1959;41-B:736–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Scott TF, Bailey RW. Idiopathic scoliosis in fraternal twins. J Mich State Med Soc. 1963;62:283–4.PubMedGoogle Scholar
  18. 18.
    Cowell HR, Hall JN, MacEwen GD. Genetic aspects of idiopathic scoliosis. A Nicholas Andry award essay, 1970. Clin Orthop Relat Res. 1972;86:121–31.CrossRefPubMedGoogle Scholar
  19. 19.
    Miller NH, Schwab DL, Sponseller P, Shugert E, Bell J, Maestri N. Genomic search for X-linkage in familial adolescent idiopathic scoliosis. In: IRSoSDMn, editor. Research into spinal deformities 2. Amsterdam: IOS Press; 1998. p. 209–13.Google Scholar
  20. 20.
    Czeizel A, Bellyei A, Barta O, Magda T, Molnar L. Genetics of adolescent idiopathic scoliosis. J Med Genet. 1978;15(6):424–7.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kruse LM, Buchan JG, Gurnett CA, Dobbs MB. Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis: the Carter effect. J Bone Joint Surg Am. 2012;94(16):1485–91.CrossRefPubMedGoogle Scholar
  22. 22.
    Robin GC, Cohen T. Familial scoliosis. A clinical report. J Bone Joint Surg Br. 1975;57(2):146–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Carr AJ, Ogilvie DJ, Wordsworth BP, Priestly LM, Smith R, Sykes B. Segregation of structural collagen genes in adolescent idiopathic scoliosis. Clin Orthop Relat Res. 1992;(274):305–10.Google Scholar
  24. 24.
    Bell M, Teebi AS. Autosomal dominant idiopathic scoliosis? Am J Med Genet. 1995;55(1):112.CrossRefPubMedGoogle Scholar
  25. 25.
    Miller NH, Mims B, Child A, Milewicz DM, Sponseller P, Blanton SH. Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis. J Orthop Res. 1996;14(6):994–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Aksenovich TI, Semenov IR, Ginzburg E, Zaidman AM. Preliminary analysis of inheritance of scoliosis. Genetika. 1988;24(11):2056–63.PubMedGoogle Scholar
  27. 27.
    Axenovich TI, Zaidman AM, Zorkoltseva IV, Tregubova IL, Borodin PM. Segregation analysis of idiopathic scoliosis: demonstration of a major gene effect. Am J Med Genet. 1999;86(4):389–94.CrossRefPubMedGoogle Scholar
  28. 28.
    Justice CM, Miller NH, Marosy B, Zhang J, Wilson AF. Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus. Spine. 2003;28(6):589–94.PubMedGoogle Scholar
  29. 29.
    Berquet KH. Considerations on heredity in idiopathic scoliosis. Z Orthop Ihre Grenzgeb. 1966;101(2):197–209.PubMedGoogle Scholar
  30. 30.
    Shapiro JR, Burn VE, Chipman SD, Velis KP, Bansal M. Osteoporosis and familial idiopathic scoliosis: association with an abnormal alpha 2(I) collagen. Connect Tissue Res. 1989;21(1–4):117–23. discussion 24CrossRefPubMedGoogle Scholar
  31. 31.
    Levaia NV. Genetic aspect of dysplastic (idiopathic) scoliosis. Ortop Travmatol Protez. 1981;(2):23–9.Google Scholar
  32. 32.
    Marosy B, Justice CM, Nzegwu N, Kumar G, Wilson AF, Miller NH. Lack of association between the aggrecan gene and familial idiopathic scoliosis. Spine. 2006;31(13):1420–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Wise CA, Barnes R, Gillum J, Herring JA, Bowcock AM, Lovett M. Localization of susceptibility to familial idiopathic scoliosis. Spine. 2000;25(18):2372–80.CrossRefPubMedGoogle Scholar
  34. 34.
    Chan V, Fong GC, Luk KD, Yip B, Lee MK, Wong MS, et al. A genetic locus for adolescent idiopathic scoliosis linked to chromosome 19p13.3. Am J Hum Genet. 2002;71(2):401–6.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Salehi LB, Mangino M, De Serio S, De Cicco D, Capon F, Semprini S, et al. Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11. Hum Genet. 2002;111(4–5):401–4.CrossRefPubMedGoogle Scholar
  36. 36.
    Miller NH, Justice CM, Marosy B, Doheny KF, Pugh E, Zhang J, et al. Identification of candidate regions for familial idiopathic scoliosis. Spine. 2005;30(10):1181–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Gao X, Gordon D, Zhang D, Browne R, Helms C, Gillum J, et al. CHD7 gene polymorphisms are associated with susceptibility to idiopathic scoliosis. Am J Hum Genet. 2007;80(5):957–65.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Tilley MK, Justice CM, Swindle K, Marosy B, Wilson AF, Miller NH. CHD7 gene polymorphisms and familial idiopathic scoliosis. Spine (Phila Pa 1976). 2013;38(22):E1432–6.CrossRefGoogle Scholar
  39. 39.
    Edery P, Margaritte-Jeannin P, Biot B, Labalme A, Bernard JC, Chastang J, et al. New disease gene location and high genetic heterogeneity in idiopathic scoliosis. Eur J Hum Genet. 2011;19(8):865–9.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Patten SA, Margaritte-Jeannin P, Bernard JC, Alix E, Labalme A, Besson A, et al. Functional variants of POC5 identified in patients with idiopathic scoliosis. J Clin Invest. 2015;125(3):1124–8.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, et al. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet. 2011;20(7):1456–66.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, et al. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet. 2011;43(12):1237–40.CrossRefPubMedGoogle Scholar
  43. 43.
    Fan YH, Song YQ, Chan D, Takahashi Y, Ikegawa S, Matsumoto M, et al. SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese. J Hum Genet. 2012;57:244–6.CrossRefPubMedGoogle Scholar
  44. 44.
    Gao W, Peng Y, Liang G, Liang A, Ye W, Zhang L, et al. Association between common variants near LBX1 and adolescent idiopathic scoliosis replicated in the Chinese Han population. PLoS One. 2013;8(1):e53234.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Jiang H, Qiu X, Dai J, Yan H, Zhu Z, Qian B, et al. Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population. Eur Spine J. 2013;22(2):282–6.CrossRefPubMedGoogle Scholar
  46. 46.
    Londono D, Kou I, Johnson TA, Sharma S, Ogura Y, Tsunoda T, et al. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. J Med Genet. 2014;51(6):401–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Grauers A, Wang J, Einarsdottir E, Simony A, Danielsson A, Akesson K, et al. Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis. Spine J. 2015;15(10):2239–46.CrossRefPubMedGoogle Scholar
  48. 48.
    Zhu Z, Tang NL, Xu L, Qin X, Mao S, Song Y, et al. Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls. Nat Commun. 2015;6:8355.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Chettier R, Nelson L, Ogilvie JW, Albertsen HM, Ward K. Haplotypes at LBX1 have distinct inheritance patterns with opposite effects in adolescent idiopathic scoliosis. PLoS One. 2015;10(2):e0117708.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Cao Y, Min J, Zhang Q, Li H, Li H. Associations of LBX1 gene and adolescent idiopathic scoliosis susceptibility: a meta-analysis based on 34,626 subjects. BMC Musculoskelet Disord. 2016;17:309.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Liu S, Wu N, Zuo Y, Zhou Y, Liu J, Liu Z, et al. Genetic polymorphism of LBX1 is associated with adolescent idiopathic scoliosis in northern Chinese Han population. Spine (Phila Pa 1976). 2017;42:1125–9.CrossRefGoogle Scholar
  52. 52.
    Nada D, Julien C, Samuels ME, Moreau A. A replication study for association of LBX1 locus with adolescent idiopathic scoliosis in French-Canadian population. Spine (Phila Pa 1976). 2017;43:172–178.CrossRefPubMedGoogle Scholar
  53. 53.
    Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, et al. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013;45(6):676–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Xu JF, Yang GH, Pan XH, Zhang SJ, Zhao C, Qiu BS, et al. Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations. Genomics. 2015;105(2):101–7.CrossRefPubMedGoogle Scholar
  55. 55.
    Qin X, Xu L, Xia C, Zhu W, Sun W, Liu Z, et al. Genetic variant of GPR126 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population. Spine (Phila Pa 1976). 2017;42:E1098–103.CrossRefGoogle Scholar
  56. 56.
    Ogura Y, Kou I, Miura S, Takahashi A, Xu L, Takeda K, et al. A functional SNP in BNC2 is associated with adolescent idiopathic scoliosis. Am J Hum Genet. 2015;97(2):337–42.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Miyake A, Kou I, Takahashi Y, Johnson TA, Ogura Y, Dai J, et al. Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3. PLoS One. 2013;8(9):e72802.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Sharma S, Londono D, Eckalbar WL, Gao X, Zhang D, Mauldin K, et al. A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nat Commun. 2015;6:6452.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Zhu Z, Xu L, Leung-Sang Tang N, Qin X, Feng Z, Sun W, et al. Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis. Hum Mol Genet. 2017;26(8):1577–83.CrossRefPubMedGoogle Scholar
  60. 60.
    Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T, et al. Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Hum Mol Genet. 2014;23:5271–82.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Baschal EE, Wethey CI, Swindle K, Baschal RM, Gowan K, Tang NL, et al. Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis. G3 (Bethesda). 2014;5(2):167–74.CrossRefGoogle Scholar
  62. 62.
    Haller G, Alvarado D, McCall K, Yang P, Cruchaga C, Harms M, et al. A polygenic burden of rare variants across extracellular matrix genes among individuals with adolescent idiopathic scoliosis. Hum Mol Genet. 2016;25(1):202–9.CrossRefPubMedGoogle Scholar
  63. 63.
    Li W, Li Y, Zhang L, Guo H, Tian D, Li Y, et al. AKAP2 identified as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis. J Med Genet. 2016;53(7):488–93.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Gao W, Chen C, Zhou T, Yang S, Gao B, Zhou H, et al. Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis. Hum Mutat. 2017;38(11):1500–10.CrossRefPubMedGoogle Scholar
  65. 65.
    Fendri K, Patten SA, Kaufman GN, Zaouter C, Parent S, Grimard G, et al. Microarray expression profiling identifies genes with altered expression in adolescent idiopathic scoliosis. Eur Spine J. 2013;22(6):1300–11.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Moreau A, Wang DS, Forget S, Azeddine B, Angeloni D, Fraschini F, et al. Melatonin signaling dysfunction in adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2004;29(16):1772–81.CrossRefGoogle Scholar
  67. 67.
    Azeddine B, Letellier K, Wang da S, Moldovan F, Moreau A. Molecular determinants of melatonin signaling dysfunction in adolescent idiopathic scoliosis. Clin Orthop Relat Res. 2007;462:45–52.CrossRefPubMedGoogle Scholar
  68. 68.
    Oliazadeh N, Gorman KF, Eveleigh R, Bourque G, Moreau A. Identification of elongated primary cilia with impaired Mechanotransduction in idiopathic scoliosis patients. Sci Rep. 2017;7:44260.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Nowak R, Kwiecien M, Tkacz M, Mazurek U. Transforming growth factor-beta (TGF- beta) signaling in paravertebral muscles in juvenile and adolescent idiopathic scoliosis. Biomed Res Int. 2014;2014:594287.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Qiu Y, Wu L, Wang B, Yu Y, Zhu Z. Asymmetric expression of melatonin receptor mRNA in bilateral paravertebral muscles in adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2007;32(6):667–72.CrossRefGoogle Scholar
  71. 71.
    Zamecnik J, Krskova L, Hacek J, Stetkarova I, Krbec M. Etiopathogenesis of adolescent idiopathic scoliosis: expression of melatonin receptors 1A/1B, calmodulin and estrogen receptor 2 in deep paravertebral muscles revisited. Mol Med Rep. 2016;14(6):5719–24.CrossRefPubMedGoogle Scholar
  72. 72.
    Buchan JG, Alvarado DM, Haller G, Aferol H, Miller NH, Dobbs MB, et al. Are copy number variants associated with adolescent idiopathic scoliosis? Clin Orthop Relat Res. 2014;472(10):3216–25.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J. Role of melatonin deficiency in the development of scoliosis in pinealectomised chickens. J Bone Joint Surg Br. 1995;77(1):134–8.CrossRefPubMedGoogle Scholar
  74. 74.
    Bagnall K, Raso VJ, Moreau M, Mahood J, Wang X, Zhao J. The effects of melatonin therapy on the development of scoliosis after pinealectomy in the chicken. J Bone Joint Surg Am. 1999;81(2):191–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Morcuende JA, Minhas R, Dolan L, Stevens J, Beck J, Wang K, et al. Allelic variants of human melatonin 1A receptor in patients with familial adolescent idiopathic scoliosis. Spine. 2003;28(17):2025–8. discussion 9CrossRefPubMedGoogle Scholar
  76. 76.
    Machida M, Murai I, Miyashita Y, Dubousset J, Yamada T, Kimura J. Pathogenesis of idiopathic scoliosis. Experimental study in rats. Spine (Phila Pa 1976). 1999;24(19):1985–9.CrossRefGoogle Scholar
  77. 77.
    Machida M, Saito M, Dubousset J, Yamada T, Kimura J, Shibasaki K. Pathological mechanism of idiopathic scoliosis: experimental scoliosis in pinealectomized rats. Eur Spine J. 2005;14(9):843–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Akel I, Kocak O, Bozkurt G, Alanay A, Marcucio R, Acaroglu E. The effect of calmodulin antagonists on experimental scoliosis: a pinealectomized chicken model. Spine (Phila Pa 1976). 2009;34(6):533–8.CrossRefGoogle Scholar
  79. 79.
    Wu T, Sun X, Zhu Z, Zheng X, Qian B, Zhu F, et al. Role of high central leptin activity in a scoliosis model created in bipedal amputated mice. Stud Health Technol Inform. 2012;176:31–5.PubMedGoogle Scholar
  80. 80.
    Yadav MC, Huesa C, Narisawa S, Hoylaerts MF, Moreau A, Farquharson C, et al. Ablation of Osteopontin improves the skeletal phenotype of Phospho1 mice. J Bone Miner Res. 2014;29:2369–81.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Boswell CW, Ciruna B. Understanding idiopathic scoliosis: a new zebrafish School of Thought. Trends Genet. 2017;33(3):183–96.CrossRefPubMedGoogle Scholar
  82. 82.
    Gorman KF, Breden F. Teleosts as models for human vertebral stability and deformity. Comp Biochem Physiol C Toxicol Pharmacol. 2007;145(1):28–38.CrossRefPubMedGoogle Scholar
  83. 83.
    Gorman KF, Breden F. Idiopathic-type scoliosis is not exclusive to bipedalism. Med Hypotheses. 2009;72(3):348–52.CrossRefPubMedGoogle Scholar
  84. 84.
    Gorman KF, Christians JK, Parent J, Ahmadi R, Weigel D, Dreyer C, et al. A major QTL controls susceptibility to spinal curvature in the curveback guppy. BMC Genet. 2011;12:16.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Buchan JG, Gray RS, Gansner JM, Alvarado DM, Burgert L, Gitlin JD, et al. Kinesin family member 6 (kif6) is necessary for spine development in zebrafish. Dev Dyn. 2014;243(12):1646–57.CrossRefPubMedGoogle Scholar
  86. 86.
    Hayes M, Gao X, Yu LX, Paria N, Henkelman RM, Wise CA, et al. ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. Nat Commun. 2014;5:4777.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Grimes DT, Boswell CW, Morante NF, Henkelman RM, Burdine RD, Ciruna B. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science. 2016;352(6291):1341–4.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Inoue M, Minami S, Nakata Y, Kitahara H, Otsuka Y, Isobe K, et al. Association between estrogen receptor gene polymorphisms and curve severity of idiopathic scoliosis. Spine. 2002;27(21):2357–62.CrossRefPubMedGoogle Scholar
  89. 89.
    Alden KJ, Marosy B, Nzegwu N, Justice CM, Wilson AF, Miller NH. Idiopathic scoliosis: identification of candidate regions on chromosome 19p13. Spine. 2006;31(16):1815–9.CrossRefPubMedGoogle Scholar
  90. 90.
    Yeung HY, Tang NL, Lee KM, Ng BK, Hung VW, Kwok R, et al. 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.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Wu J, Qiu Y, Zhang L, Sun Q, Qiu X, He Y. Association of estrogen receptor gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine. 2006;31(10):1131–6.CrossRefPubMedGoogle Scholar
  92. 92.
    Tang NL, Yeung HY, Lee KM, Hung VW, Cheung CS, Ng BK, et al. A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases. Spine. 2006;31(21):2463–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Qiu XS, Tang NL, Yeung HY, Qiu Y, Qin L, Lee KM, et al. The role of melatonin receptor 1B gene (MTNR1B) in adolescent idiopathic scoliosis--a genetic association study. Stud Health Technol Inform. 2006;123:3–8.PubMedGoogle Scholar
  94. 94.
    Montanaro L, Parisini P, Greggi T, Di Silvestre M, Campoccia D, Rizzi S, et al. Evidence of a linkage between matrilin-1 gene (MATN1) and idiopathic scoliosis. Scoliosis. 2006;1:21.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Ocaka L, Zhao C, Reed JA, Ebenezer ND, Brice G, Morley T, et al. Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel. J Med Genet. 2008;45(2):87–92.CrossRefPubMedGoogle Scholar
  96. 96.
    Raggio CL, Giampietro PF, Dobrin S, Zhao C, Dorshorst D, Ghebranious N, et al. A novel locus for adolescent idiopathic scoliosis on chromosome 12p. J Orthop Res. 2009;27(10):1366–72.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Marosy B, Justice C, Vu C, Zorn A, Nzegwu N, Wilson A, et al. Identification of susceptibility loci for scoliosis in FIS families with triple curves. AJMG. 2010;152A:846–55.Google Scholar
  98. 98.
    Clough M, Justice CM, Marosy B, Miller NH. Males with familial idiopathic scoliosis: a distinct phenotypic subgroup. Spine (Phila Pa 1976). 2010;35(2):162–8.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Elizabeth A. Terhune
    • 1
  • Erin E. Baschal
    • 1
  • Nancy Hadley Miller
    • 1
    • 2
    Email author
  1. 1.Department of OrthopedicsUniversity of Colorado Anschutz Medical CampusAuroraUSA
  2. 2.Musculoskeletal Research Center, Children’s Hospital ColoradoAuroraUSA

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