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Current Understanding of Genetic Factors in Idiopathic Scoliosis

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The Genetics and Development of Scoliosis

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Abstract

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting 2–3% of children worldwide, yet its biologic origins are poorly understood. Epidemiology studies predict that susceptibility to AIS is mostly due to genetic factors that may differ between the sexes, as girls are at significantly greater risk of progressive disease than boys. The advent of affordable yet powerful next-generation sequencing technologies, very large reference datasets, and other publicly available tools and resources is essential for solving the complex genetic architecture of AIS. A small fraction of the total genetic risk in AIS has been discovered to date, mostly by population-based genome-wide association studies (GWAS) that correlate common polymorphisms with disease. Several validated loci point to noncoding regulatory elements that may regulate early spinal development. Rare variants are also expected to contribute to disease risk and are discoverable by well-powered sequence-based approaches. The ability to scale genetic studies through emerging technologies and consortium-sponsored collaboration will be key to defining the full genetic architecture of AIS and identifying biologic networks that may be therapeutically targetable. A second important goal of AIS research is to leverage genetic and clinical information to predict individual disease risk, risk of progression, and response to treatment.

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References

  1. Appleby J, Mitchell PD, Robinson C, Brough A, Rutty G, Harris RA, et al. The scoliosis of Richard III, last Plantagenet King of England: diagnosis and clinical significance. Lancet. 2014;383(9932):1944.

    Article  PubMed  Google Scholar 

  2. Herring J, editor. Tachdjian’s Pediatric Orthopaedics. 5th ed. Philadelphia: WB Saunders; 2013.

    Google Scholar 

  3. Hresko MT. Clinical practice. Idiopathic scoliosis in adolescents. N Engl J Med. 2013;368(9):834–41.

    Article  CAS  PubMed  Google Scholar 

  4. Carter CO, Evans KA. Inheritance of congenital pyloric stenosis. J Med Genet. 1969;6(3):233–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

  6. Antonarakis SE, Chakravarti A, Cohen JC, Hardy J. Mendelian disorders and multifactorial traits: the big divide or one for all? Nat Rev Genet. 2010;11(5):380–4.

    Article  CAS  PubMed  Google Scholar 

  7. Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008;322(5903):881–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Spielman RS, Ewens WJ. The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet. 1996;59(5):983–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  9. Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, Bagoutdinov R, et al. The NCBI dbGaP database of genotypes and phenotypes. Nat Genet. 2007;39(10):1181–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tryka KA, Hao L, Sturcke A, Jin Y, Wang ZY, Ziyabari L, et al. NCBI's Database of Genotypes and Phenotypes: dbGaP. Nucleic Acids Res. 2014;42(Database issue):D975–9.

    Article  CAS  PubMed  Google Scholar 

  11. Freathy RM, Mook-Kanamori DO, Sovio U, Prokopenko I, Timpson NJ, Berry DJ, et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010;42(5):430–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hirata MNA, Kamatani Y, Ninomiya T, Tamakoshi A, Yamagata Z, Kubo M, Muto K, Kiyohara Y, Mushiroda T, Murakami Y, Yuji K, Furukawa Y, Zembutsu H, Tanaka T, Ohnishi Y, Nakamura Y, BioBank Japan Coperative Hospital Group, Matsuda K. Overview of BioBank Japan follow-up data in 32 diseases. J Epidemiol. 2017;27(3S):S22–S8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pasaniuc B, Price AL. Dissecting the genetics of complex traits using summary association statistics. Nat Rev Genet. 2017;18(2):117–27.

    Article  CAS  PubMed  Google Scholar 

  15. Hindorff LA, Junkins H.A, Mehta JP, Manolio TA. A Catalog of Published Genome-Wide Association Studies. Available at: http://www.genome.gov/gwastudies. Accessed [date of access].

  16. Hindorff LA, Morales J (European Bioinformatics Institute), Junkins HA, Hall PN, Klemm AK, and Manolio TA. A Catalog of Published Genome-Wide Association Studies. Available from: http://www.genome.gov/gwastudies.

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Londono D, et al. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. J Med Genet. 2014;6:401–6.

    Article  CAS  Google Scholar 

  21. Jagla K, Frasch M, Jagla T, Dretzen G, Bellard F, Bellard M. Ladybird, a new component of the cardiogenic pathway in Drosophila required for diversification of heart precursors. Development. 1997;124(18):3471–9.

    PubMed  CAS  Google Scholar 

  22. Jagla K, Jagla T, Heitzler P, Dretzen G, Bellard F, Bellard M. Ladybird, a tandem of homeobox genes that maintain late wingless expression in terminal and dorsal epidermis of the Drosophila embryo. Development. 1997;124(1):91–100.

    PubMed  CAS  Google Scholar 

  23. Jagla K, Dolle P, Mattei MG, Jagla T, Schuhbaur B, Dretzen G, et al. Mouse Lbx1 and human LBX1 define a novel mammalian homeobox gene family related to the Drosophila lady bird genes. Mech Dev. 1995;53(3):345–56.

    Article  CAS  PubMed  Google Scholar 

  24. Gross MK, Moran-Rivard L, Velasquez T, Nakatsu MN, Jagla K, Goulding M. Lbx1 is required for muscle precursor migration along a lateral pathway into the limb. Development. 2000;127(2):413–24.

    PubMed  CAS  Google Scholar 

  25. Brohmann H, Jagla K, Birchmeier C. The role of Lbx1 in migration of muscle precursor cells. Development. 2000;127(2):437–45.

    PubMed  CAS  Google Scholar 

  26. Schafer K, Neuhaus P, Kruse J, Braun T. The homeobox gene Lbx1 specifies a subpopulation of cardiac neural crest necessary for normal heart development. Circ Res. 2003;92(1):73–80.

    Article  PubMed  Google Scholar 

  27. Gross MK, Dottori M, Goulding M. Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron. 2002;34(4):535–49.

    Article  CAS  PubMed  Google Scholar 

  28. Muller T, Brohmann H, Pierani A, Heppenstall PA, Lewin GR, Jessell TM, et al. The homeodomain factor lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord. Neuron. 2002;34(4):551–62.

    Article  CAS  PubMed  Google Scholar 

  29. Guo L, Yamashita H, Kou I, Takimoto A, Meguro-Horike M, Horike S, et al. Functional investigation of a non-coding variant associated with adolescent idiopathic scoliosis in zebrafish: elevated expression of the ladybird homeobox gene causes body axis deformation. PLoS Genet. 2016;12(1):e1005802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 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;45:676–9.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. Soranzo N, Rivadeneira F, Chinappen-Horsley U, Malkina I, Richards JB, Hammond N, et al. Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size. PLoS Genet. 2009;5(4):e1000445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shukunami C, Shigeno C, Atsumi T, Ishizeki K, Suzuki F, Hiraki Y. Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor. J Cell Biol. 1996;133(2):457–68.

    Article  CAS  PubMed  Google Scholar 

  34. Ikegawa S. Genomic study of adolescent idiopathic scoliosis in Japan. Scoliosis Spinal Disord. 2016;11:5.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Langenhan T, Aust G, Hamann J. Sticky signaling--adhesion class g protein-coupled receptors take the stage. Sci Signal. 2013;6(276):re3.

    Article  CAS  PubMed  Google Scholar 

  36. Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR, Dominguez C, et al. A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science. 2009;325(5946):1402–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Monk KR, Oshima K, Jors S, Heller S, Talbot WS. Gpr126 is essential for peripheral nerve development and myelination in mammals. Development. 2011;138(13):2673–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Waller-Evans H, Promel S, Langenhan T, Dixon J, Zahn D, Colledge WH, et al. The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse. PLoS One. 2010;5(11):e14047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Geng FS, Abbas L, Baxendale S, Holdsworth CJ, Swanson AG, Slanchev K, et al. Semicircular canal morphogenesis in the zebrafish inner ear requires the function of gpr126 (lauscher), an adhesion class G protein-coupled receptor gene. Development. 2013;140(21):4362–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Karner CM, Long F, Solnica-Krezel L, Monk KR, Gray RS. Gpr126/Adgrg6 deletion in cartilage models idiopathic scoliosis and pectus excavatum in mice. Hum Mol Genet. 2015;24(15):4365–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. Wallin J, Wilting J, Koseki H, Fritsch R, Christ B, Balling R. The role of Pax-1 in axial skeleton development. Development. 1994;120(5):1109–21.

    PubMed  CAS  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. Bharti S, Handrow-Metzmacher H, Zickenheiner S, Zeitvogel A, Baumann R, Starzinski-Powitz A. Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarized epithelial cells. Mol Biol Cell. 2004;15(1):397–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Schubert FR, Tremblay P, Mansouri A, Faisst AM, Kammandel B, Lumsden A, et al. Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites. Dev Dyn. 2001;222(3):506–21.

    Article  CAS  PubMed  Google Scholar 

  47. Buckingham M, Relaix F. The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions. Annu Rev Cell Dev Biol. 2007;23:645–73.

    Article  CAS  PubMed  Google Scholar 

  48. Young AP, Wagers AJ. Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors. J Cell Sci. 2010;123(Pt 15):2632–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Relaix F, Rocancourt D, Mansouri A, Buckingham M. A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. Nature. 2005;435(7044):948–53.

    Article  CAS  PubMed  Google Scholar 

  50. Kullander K, Butt SJ, Lebret JM, Lundfald L, Restrepo CE, Rydstrom A, et al. Role of EphA4 and EphrinB3 in local neuronal circuits that control walking. Science. 2003;299(5614):1889–92.

    Article  CAS  PubMed  Google Scholar 

  51. Farlie PG, Dringen R, Rees SM, Kannourakis G, Bernard O. bcl-2 transgene expression can protect neurons against developmental and induced cell death. Proc Natl Acad Sci U S A. 1995;92(10):4397–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Moriishi T, Maruyama Z, Fukuyama R, Ito M, Miyazaki T, Kitaura H, et al. Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis. PLoS One. 2011;6(11):e27487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 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 (Phila Pa 1976). 2006;31(10):1131–6.

    Article  Google Scholar 

  54. Zhang HQ, Lu SJ, Tang MX, Chen LQ, Liu SH, Guo CF, et al. Association of estrogen receptor beta gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2009;34(8):760–4.

    Article  CAS  Google Scholar 

  55. Chen Z, Tang NL, Cao X, Qiao D, Yi L, Cheng JC, et al. Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population. Eur J Hum Genet. 2009;17(4):525–32.

    Article  CAS  PubMed  Google Scholar 

  56. 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.

    PubMed  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Dy P, Wang W, Bhattaram P, Wang Q, Wang L, Ballock RT, et al. Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev Cell. 2012;22(3):597–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Liu CF, Lefebvre V. The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis. Nucleic Acids Res. 2015;43(17):8183–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lekovic GP, Rekate HL, Dickman CA, Pearson M. Congenital cervical instability in a patient with camptomelic dysplasia. Child’s Nerv Syst. 2006;22(9):1212–4.

    Article  Google Scholar 

  61. Henry SP, Liang S, Akdemir KC, de Crombrugghe B. The postnatal role of Sox9 in cartilage. J Bone Miner Res. 2012;27(12):2511–25.

    Article  CAS  PubMed  Google Scholar 

  62. Wunderle VM, Critcher R, Hastie N, Goodfellow PN, Schedl A. Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia. Proc Natl Acad Sci U S A. 1998;95(18):10649–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gordon CT, Tan TY, Benko S, Fitzpatrick D, Lyonnet S, Farlie PG. Long-range regulation at the SOX9 locus in development and disease. J Med Genet. 2009;46(10):649–56.

    Article  CAS  PubMed  Google Scholar 

  64. Zhang X, Cowper-Sal lari R, Bailey SD, Moore JH, Lupien M. Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus. Genome Res. 2012;22(8):1437–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tristani-Firouzi M, Etheridge SP. Kir 2.1 channelopathies: the Andersen-Tawil syndrome. Pflugers Arch. 2010;460(2):289–94.

    Article  CAS  PubMed  Google Scholar 

  66. Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen’s syndrome. Cell. 2001;105(4):511–9.

    Article  CAS  PubMed  Google Scholar 

  67. Lestner JM, Ellis R, Canham N. Delineating the 17q24.2-q24.3 microdeletion syndrome phenotype. Eur J Med Genet. 2012;55(12):700–4.

    Article  PubMed  Google Scholar 

  68. Blyth M, Huang S, Maloney V, Crolla JA, Karen Temple I. A 2.3Mb deletion of 17q24.2-q24.3 associated with ‘Carney complex plus’. Eur J Med Genet. 2008;51(6):672–8.

    Article  PubMed  Google Scholar 

  69. KI OY, Takahashi Y, Takeda K, Minami S, Kawakami N, Uno K, Ito M, Yonezawa I, Kaito T, Yanagida H, Watanabe K, Taneichi H, Harimaya K, Taniguchi Y, Kotani T, Tsuji T, Suzuki T, Sudo H, Fujita N, Yagi M, Chiba K, Kubo M, Kamatani Y, Nakamura M, Matsumoto M, Japan Scoliosis Clinical Research Group, Watanabe K, Ikegawa S, Japan Scoliosis Clinical Research Group. A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis. Hum Mol Genet. 2017;26(20):4086–92.

    Article  CAS  Google Scholar 

  70. Weinstein SL. Natural history. Spine (Phila Pa 1976). 1999;24(24):2592–600.

    Article  CAS  Google Scholar 

  71. Carman DL, Browne RH, Birch JG. Measurement of scoliosis and kyphosis radiographs. Intraobserver and interobserver variation. J Bone Joint Surg. 1990;72(3):328–33.

    Article  CAS  PubMed  Google Scholar 

  72. Londono D, Chen KM, Musolf A, Wang R, Shen T, Brandon J, et al. A novel method for analyzing genetic association with longitudinal phenotypes. Stat Appl Genet Mol Biol. 2013;12(2):241–61.

    Article  PubMed  Google Scholar 

  73. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chatterjee S, Ahituv N. Gene regulatory elements, major drivers of human disease. Annu Rev Genomics Hum Genet. 2017;18:45–63.

    Article  CAS  PubMed  Google Scholar 

  75. Lee S, Emond MJ, Bamshad MJ, Barnes KC, Rieder MJ, Nickerson DA, et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am J Hum Genet. 2012;91(2):224–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Consortium EP, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74.

    Article  CAS  Google Scholar 

  77. 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(19):5271–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–85.

    Article  CAS  PubMed  Google Scholar 

  79. 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.

    Article  CAS  PubMed  Google Scholar 

  80. Project e. Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease. Nat Genet. 2017;49:1664–70.

    Article  CAS  Google Scholar 

  81. Grun D, van Oudenaarden A. Design and analysis of single-cell sequencing experiments. Cell. 2015;163(4):799–810.

    Article  CAS  PubMed  Google Scholar 

  82. Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P. Maternal uniparental disomy for chromosome 14. J Med Genet. 1991;28(8):511–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet. 2016;387(10014):156–67.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Felix MA, Barkoulas M. Pervasive robustness in biological systems. Nat Rev Genet. 2015;16(8):483–96.

    Article  CAS  PubMed  Google Scholar 

  85. 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.

    Article  CAS  PubMed  Google Scholar 

  86. Giampietro PF, Pourquié O, Raggio C, Ikegawa S, Turnpenny PD, Gray R, et al. Summary of the first inaugural joint meeting of the International Consortium for scoliosis genetics and the International Consortium for Vertebral Anomalies and Scoliosis, March 16–18, 2017, Dallas, Texas. Am J Med Genet A. 2017;176(1):253–6.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the patients, families, and other individuals who have participated in AIS genetic research studies. We also thank Sarah Lassen from the Media Department at Texas Scottish Rite Hospital for Children for helping with figures.

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Authors and Affiliations

  1. Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, TX, USA

    Carol A. Wise

  2. Departments of Orthopaedic Surgery, Pediatrics, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Carol A. Wise

  3. Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan

    Shiro Ikegawa

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Correspondence to Carol A. Wise .

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Editors and Affiliations

  1. School of Life Sciences, Arizona State University, Tempe, Arizona, USA

    Kenro Kusumi

  2. Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, Australia

    Sally L. Dunwoodie

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Wise, C.A., Ikegawa, S. (2018). Current Understanding of Genetic Factors in Idiopathic Scoliosis. In: Kusumi, K., Dunwoodie, S. (eds) The Genetics and Development of Scoliosis. Springer, Cham. https://doi.org/10.1007/978-3-319-90149-7_6

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