Skip to main content

Advertisement

Log in

Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

A CORR Insights to this article was published on 29 July 2014

Abstract

Background

Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder that causes spinal deformity in approximately 3% of the population. Candidate gene, linkage, and genome-wide association studies have sought to identify genetic variation that predisposes individuals to AIS, but the genetic basis remains unclear. Copy number variants are associated with several isolated skeletal phenotypes, but their role in AIS, to our knowledge, has not been assessed.

Questions/Purposes

We determined the frequency of recurrent copy number rearrangements, chromosome aneuploidy, and rare copy number variants in patients with AIS.

Methods

Between January 2010 and August 2014, we evaluated 150 patients with isolated AIS and spinal curvatures measuring 10° or greater, and 148 agreed to participate. Genomic copy number analysis was performed on patients and 1079 control subjects using the Affymetrix® Genome-wide Human SNP Array 6.0. After removing poor quality samples, 143 (97%) patients with AIS were evaluated for copy number variation.

Results

We identified a duplication of chromosome 1q21.1 in 2.1% (N = 3/143) of patients with AIS, which was enriched compared with 0.09% (N = 1/1079) of control subjects (p = 0.0057) and 0.07% (N = 6/8329) of a large published control cohort (p = 0.0004). Other notable findings include trisomy X, which was identified in 1.8% (N = 2/114) of female patients with AIS, and rearrangements of chromosome 15q11.2 and 16p11.2 that previously have been associated with spinal phenotypes. Finally, we report rare copy number variants that will be useful in future studies investigating candidate genes for AIS.

Conclusions

Copy number variation and chromosomal aneuploidy may contribute to the pathogenesis of adolescent idiopathic scoliosis.

Clinical Relevance

Chromosomal microarray may reveal clinically useful abnormalities in some patients with AIS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1A–B

Similar content being viewed by others

References

  1. Abdelmoity AT, LePichon JB, Nyp SS, Soden SE, Daniel CA, Yu S. 15q11.2 proximal imbalances associated with a diverse array of neuropsychiatric disorders and mild dysmorphic features. J Dev Behav Pediatr. 2012;33:570–576.

    Article  PubMed  Google Scholar 

  2. Al-Kateb H, Khanna G, Filges I, Hauser N, Grange DK, Shen J, Smyser CD, Kulkarni S, Shinawi M. Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement. Am J Med Genet A. 2014;164A:1118–1126.

    Article  PubMed  Google Scholar 

  3. Albers CA, Paul DS, Schulze H, Freson K, Stephens JC, Smethurst PA, Jolley JD, Cvejic A, Kostadima M, Bertone P, Breuning MH, Debili N, Deloukas P, Favier R, Fiedler J, Hobbs CM, Huang N, Hurles ME, Kiddle G, Krapels I, Nurden P, Ruivenkamp CA, Sambrook JG, Smith K, Stemple DL, Strauss G, Thys C, van Geet C, Newbury-Ecob R, Ouwehand WH, Ghevaert C. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat Genet. 2012;44:435–439.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Alvarado DM, Aferol H, McCall K, Huang JB, Techy M, Buchan J, Cady J, Gonzales PR, Dobbs MB, Gurnett CA. Familial isolated clubfoot is associated with recurrent chromosome 17q23.1q23.2 microduplications containing TBX4. Am J Hum Genet. 2010;87:154–160.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Alvarado DM, Buchan JG, Frick SL, Herzenberg JE, Dobbs MB, Gurnett CA. Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development. Eur J Hum Genet. 2013;21:373–380.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Alvarado DM, McCall K, Aferol H, Silva MJ, Garbow JR, Spees WM, Patel T, Siegel M, Dobbs MB, Gurnett CA. Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice. Hum Mol Genet. 2011;20:3943–3952.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Barr ML, Sergovich FR, Carr DH, Saver EL. The triplo-X female: an appraisal based on a study of 12 cases and a review of the literature. Can Med Assoc J. 1969;101:247–258.

    PubMed  CAS  PubMed Central  Google Scholar 

  8. Bijlsma EK, Gijsbers AC, Schuurs-Hoeijmakers JH, van Haeringen A, Fransen van de Putte DE, Anderlid BM, Lundin J, Lapunzina P, Perez Jurado LA, Delle Chiaie B, Loeys B, Menten B, Oostra A, Verhelst H, Amor DJ, Bruno DL, van Essen AJ, Hordijk R, Sikkema-Raddatz B, Verbruggen KT, Jongmans MC, Pfundt R, Reeser HM, Breuning MH, Ruivenkamp CA. Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals. Eur J Med Genet. 2009;52:77–87.

  9. Brunet A, Armengol L, Heine D, Rosell J, Garcia-Aragones M, Gabau E, Estivill X, Guitart M. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1. BMC Med Genet. 2009;10:144.

    Article  PubMed  PubMed Central  Google Scholar 

  10. CDC Centers for Disease Control and Prevention. National Center for Health Statistics. Health, United States, 2013. Available at: http://www.cdc.gov/nchs/. Accessed January 3, 2014.

  11. Chew S, Dastani Z, Brown SJ, Lewis JR, Dudbridge F, Soranzo N, Surdulescu GL, Richards JB, Spector TD, Wilson SG. Copy number variation of the APC gene is associated with regulation of bone mineral density. Bone. 2012;51:939–943.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Cobb JR. Outline for the study of scoliosis. Instr Course Lect. 1948;5:261–265.

    Google Scholar 

  13. Cook EH Jr, Scherer SW. Copy-number variations associated with neuropsychiatric conditions. Nature. 2008;455:919–923.

    Article  PubMed  CAS  Google Scholar 

  14. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE. A copy number variation morbidity map of developmental delay. Nat Genet. 2011;43:838–846.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Dick DM, Foroud T, Flury L, Bowman ES, Miller MJ, Rau NL, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Hahn R, Widmark C, McKinney R, Sutton L, Ballas C, Grice D, Berrettini W, Byerley W, Coryell W, DePaulo R, MacKinnon DF, Gershon ES, Kelsoe JR, McMahon FJ, McInnis M, Murphy DL, Reich T, Scheftner W, Nurnberger JI Jr. Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative. Am J Hum Genet. 2003;73:107–114.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Fernandez BA, Roberts W, Chung B, Weksberg R, Meyn S, Szatmari P, Joseph-George AM, Mackay S, Whitten K, Noble B, Vardy C, Crosbie V, Luscombe S, Tucker E, Turner L, Marshall CR, Scherer SW. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet. 2010;47:195–203.

    Article  PubMed  Google Scholar 

  17. Gorman KF, Julien C, Moreau A. The genetic epidemiology of idiopathic scoliosis. Eur Spine J. 2012;21:1905–1919.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gustavson KH. [Triple X syndrome deviation with mild symptoms: the majority goes undiagnosed][in Swedish]. Lakartidningen. 1999;96:5646–5647.

    PubMed  CAS  Google Scholar 

  19. Hernando C, Plaja A, Rigola MA, Perez MM, Vendrell T, Egocue J, Fuster C. Comparative genomic hybridisation shows a partial de novo deletion 16p11.2 in a neonate with multiple congenital malformations. J Med Genet. 2002;39:E24.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Hitz MP, Lemieux-Perreault LP, Marshall C, Feroz-Zada Y, Davies R, Yang SW, Lionel AC, D’Amours G, Lemyre E, Cullum R, Bigras JL, Thibeault M, Chetaille P, Montpetit A, Khairy P, Overduin B, Klaassen S, Hoodless P, Awadalla P, Hussin J, Idaghdour Y, Nemer M, Stewart AF, Boerkoel C, Scherer SW, Richter A, Dube MP, Andelfinger G. Rare copy number variants contribute to congenital left-sided heart disease. PLoS Genet. 2012;8:e1002903.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Huang N, Lee I, Marcotte EM, Hurles ME. Characterising and predicting haploinsufficiency in the human genome. PLoS Genet. 2010;6:e1001154.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kaminsky EB, Kaul V, Paschall J, Church DM, Bunke B, Kunig D, Moreno-De-Luca D, Moreno-De-Luca A, Mulle JG, Warren ST, Richard G, Compton JG, Fuller AE, Gliem TJ, Huang S, Collinson MN, Beal SJ, Ackley T, Pickering DL, Golden DM, Aston E, Whitby H, Shetty S, Rossi MR, Rudd MK, South ST, Brothman AR, Sanger WG, Iyer RK, Crolla JA, Thorland EC, Aradhya S, Ledbetter DH, Martin CL. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med. 2011;13:777–784.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kesling KL, Reinker KA. Scoliosis in twins: a meta-analysis of the literature and report of six cases. Spine (Phila Pa 1976). 1997;22:2009–2014; discussion 2015.

  24. Klopocki E, Schulze H, Strauss G, Ott CE, Hall J, Trotier F, Fleischhauer S, Greenhalgh L, Newbury-Ecob RA, Neumann LM, Habenicht R, Konig R, Seemanova E, Megarbane A, Ropers HH, Ullmann R, Horn D, Mundlos S. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet. 2007;80:232–240.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, Qiu X, Sharma S, Takimoto A, Ogura Y, Jiang H, Yan H, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Hosono N, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Londono D, Gordon D, Herring JA, Watanabe K, Chiba K, Kamatani N, Jiang Q, Hiraki Y, Kubo M, Toyama Y, Tsunoda T, Wise CA, Qiu Y, Shukunami C, Matsumoto M, Ikegawa S. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013;45:676–679.

    Article  PubMed  CAS  Google Scholar 

  26. Kouwenhoven JW, Castelein RM. The pathogenesis of adolescent idiopathic scoliosis: review of the literature. Spine (Phila Pa 1976). 2008;33:2898–2908.

  27. 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;94:1485–1491.

    Article  PubMed  Google Scholar 

  28. Ledig S, Schippert C, Strick R, Beckmann MW, Oppelt PG, Wieacker P. Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril. 2011;95:1589–1594.

    Article  PubMed  CAS  Google Scholar 

  29. Lenke L, Dobbs MB. Idiopathic scoliosis. In: Frymoyer JW, Wiesel SW, eds. The Adult and Pediatric Spine. Philadelphia, PA: Lippincott, Williams & Wilkins; 2004;337–360.

  30. Liao C, Fu F, Yi CX, Li R, Yang X, Xu Q, Li DZ. Prenatal diagnosis of an atypical 1q21.1 microdeletion and duplication associated with foetal urogenital abnormalities. Gene. 2012;507:92–94.

    Article  PubMed  CAS  Google Scholar 

  31. Linden MG, Bender BG, Harmon RJ, Mrazek DA, Robinson A. 47,XXX: what is the prognosis? Pediatrics. 1988;82:619–630.

    PubMed  CAS  Google Scholar 

  32. MacDonald JR, Ziman R, Yuen RK, Feuk L, Scherer SW. The Database of Genomic Variants: a curated collection of structural variation in the human genome. Nucleic Acids Res. 2014;42(Database issue):D986–992.

  33. Miller NH. Cause and natural history of adolescent idiopathic scoliosis. Orthop Clin North Am. 1999;30:343–352.

    Article  PubMed  CAS  Google Scholar 

  34. Miller NH. Genetics of familial idiopathic scoliosis. Clin Orthop Relat Res. 2007;462:6–10.

    Article  PubMed  Google Scholar 

  35. Miller NH. Idiopathic scoliosis: cracking the genetic code and what does it mean? J Pediatr Orthop. 2011;31(1 suppl):S49–52.

    Article  PubMed  Google Scholar 

  36. Miller NH, Justice CM, Marosy B, Doheny KF, Pugh E, Zhang J, Dietz HC 3rd, Wilson AF. Identification of candidate regions for familial idiopathic scoliosis. Spine (Phila Pa 1976). 2005;30:1181–1187.

  37. Miller NH, Justice CM, Marosy B, Swindle K, Kim Y, Roy-Gagnon MH, Sung H, Behneman D, Doheny KF, Pugh E, Wilson AF. Intra-familial tests of association between familial idiopathic scoliosis and linked regions on 9q31.3–q34.3 and 16p12.3–q22.2. Hum Hered. 2012;74:36–44.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Morrow EM. Genomic copy number variation in disorders of cognitive development. J Am Acad Child Adolesc Psychiatry. 2010;49:1091–1104.

    PubMed  PubMed Central  Google Scholar 

  39. NCBI. Build 36 (hg18). Available at: http://www.ncbi.nlm.nih.gov/mapview/stats/BuildStats.cgi?taxid=9606&build=36&ver=1. Accessed 04 Jan 2014.

  40. Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87:81–83.

    Article  CAS  Google Scholar 

  41. Olanders S. Females with Supernumerary X Chromosomes; A Study of 39 Psychiatric Cases, Stockholm, Sweden: Esselte Studium; 1977;12–16.

    Google Scholar 

  42. Otter M, Schrander-Stumpel CT, Curfs LM. Triple X syndrome: a review of the literature. Eur J Hum Genet. 2010;18:265–271.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Reamy BV, Slakey JB. Adolescent idiopathic scoliosis: review and current concepts. Am Fam Physician. 2001;64:111–116.

    PubMed  CAS  Google Scholar 

  44. Riseborough EJ, Wynne-Davies R. A genetic survey of idiopathic scoliosis in Boston, Massachusetts. J Bone Joint Surg Am. 1973;55:974–982.

    PubMed  CAS  Google Scholar 

  45. Rosenfeld JA, Coe BP, Eichler EE, Cuckle H, Shaffer LG. Estimates of penetrance for recurrent pathogenic copy-number variations. Genet Med. 2013;15:478–481.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Rosenfeld JA, Traylor RN, Schaefer GB, McPherson EW, Ballif BC, Klopocki E, Mundlos S, Shaffer LG, Aylsworth AS; 1q21.1 Study Group. Proximal microdeletions and microduplications of 1q21.1 contribute to variable abnormal phenotypes. Eur J Hum Genet. 2012;20:754–761.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  47. Schaaf CP, Goin-Kochel RP, Nowell KP, Hunter JV, Aleck KA, Cox S, Patel A, Bacino CA, Shinawi M. Expanding the clinical spectrum of the 16p11.2 chromosomal rearrangements: three patients with syringomyelia. Eur J Hum Genet. 2011;19:152–156.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, Brandon JM, Zhang D, Li QZ, Dobbs MB, Gurnett CA, Grant SF, Hakonarson H, Dormans JP, Herring JA, Gordon D, Wise CA. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet. 2011;20:1456–1466.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Shen Y, Chen X, Wang L, Guo J, Shen J, An Y, Zhu H, Zhu Y, Xin R, Bao Y, Gusella JF, Zhang T, Wu BL. Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family. Am J Med Genet B Neuropsychiatr Genet. 2011;156:225–232.

    Article  PubMed  Google Scholar 

  50. Shen Y, Dies KA, Holm IA, Bridgemohan C, Sobeih MM, Caronna EB, Miller KJ, Frazier JA, Silverstein I, Picker J, Weissman L, Raffalli P, Jeste S, Demmer LA, Peters HK, Brewster SJ, Kowalczyk SJ, Rosen-Sheidley B, McGowan C, Duda AW 3rd, Lincoln SA, Lowe KR, Schonwald A, Robbins M, Hisama F, Wolff R, Becker R, Nasir R, Urion DK, Milunsky JM, Rappaport L, Gusella JF, Walsh CA, Wu BL, Miller DT, Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. 2010;125:e727–735.

  51. Shimojima K, Inoue T, Fujii Y, Ohno K, Yamamoto T. A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and hemivertebrae. Eur J Med Genet. 2009;52:433–435.

    Article  PubMed  Google Scholar 

  52. Shin JH, Ha KY, Jung SH, Chung YJ. Genetic predisposition in degenerative lumbar scoliosis due to the copy number variation. Spine (Phila Pa 1976). 2011;36:1782–1793.

  53. Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, Scott DA, Probst FJ, Craigen WJ, Graham BH, Pursley A, Clark G, Lee J, Proud M, Stocco A, Rodriguez DL, Kozel BA, Sparagana S, Roeder ER, McGrew SG, Kurczynski TW, Allison LJ, Amato S, Savage S, Patel A, Stankiewicz P, Beaudet AL, Cheung SW, Lupski JR. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010;47:332–341.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Stankiewicz P, Lupski JR. Structural variation in the human genome and its role in disease. Annu Rev Med. 2010;61:437–455.

    Article  PubMed  CAS  Google Scholar 

  55. Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Hosono N, Kamatani N, Tsunoda T, Toyama Y, Kubo M, Matsumoto M, Ikegawa S. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet. 2011;43:1237–1240.

    Article  PubMed  CAS  Google Scholar 

  56. The International HapMap Consortium. The International HapMap Project. Nature. 2003;426:789–796.

    Article  Google Scholar 

  57. van Duyvenvoorde HA, Lui JC, Kant SG, Oostdijk W, Gijsbers AC, Hoffer MJ, Karperien M, Walenkamp MJ, Noordam C, Voorhoeve PG, Mericq V, Pereira AM, Claahsen-van de Grinten HL, van Gool SA, Breuning MH, Losekoot M, Baron J, Ruivenkamp CA, Wit JM. Copy number variants in patients with short stature. Eur J Hum Genet. 2014;22:602–609.

  58. Wang WJ, Yeung HY, Chu WC, Tang NL, Lee KM, Qiu Y, Burwell RG, Cheng JC. Top theories for the etiopathogenesis of adolescent idiopathic scoliosis. J Pediatr Orthop. 2011;31(1 suppl):S14–27.

    Article  PubMed  Google Scholar 

  59. Warburton D, Ronemus M, Kline J, Jobanputra V, Williams I, Anyane-Yeboa K, Chung W, Yu L, Wong N, Awad D, Yu CY, Leotta A, Kendall J, Yamrom B, Lee YH, Wigler M, Levy D. The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease. Hum Genet. 2014; 133:11–27.

    Article  PubMed  Google Scholar 

  60. Ward K, Ogilvie J, Argyle V, Nelson L, Meade M, Braun J, Chettier R. Polygenic inheritance of adolescent idiopathic scoliosis: a study of extended families in Utah. Am J Med Genet A. 2010;152A:1178–1188.

    Article  PubMed  Google Scholar 

  61. Wynne-Davies R. Familial (idiopathic) scoliosis: a family survey. J Bone Joint Surg Br. 1968;50:24–30.

    PubMed  CAS  Google Scholar 

  62. Zahnleiter D, Uebe S, Ekici AB, Hoyer J, Wiesener A, Wieczorek D, Kunstmann E, Reis A, Doerr HG, Rauch A, Thiel CT. Rare copy number variants are a common cause of short stature. PLoS Genet. 2013;9:e1003365.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Drs. Keith Bridwell, Lawrence Lenke, and Scott Luhmann for allowing us to recruit patients from their clinics. We thank the patients and their families for their role in this work. The Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine processed the microarrays. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant #UL1RR024992 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. The control dataset used for the analysis described in this manuscript was obtained from the database of Genotype and Phenotype (dbGaP) (http://www.ncbi.nlm.nih.gov/gap) through dbGaP accession number phs000017.v3.p1. Data for control samples were provided by John R Kelsoe and John Nurnberger as part of the NIMH Bipolar Genetics Collaborative. Control samples were genotyped through the Genetic Association Information Network (GAIN). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christina A. Gurnett MD, PhD.

Additional information

Funding for this project was provided by National Institutes of Health (NIH, K12 HD001459-08), Shriners Hospital for Children, and the Children’s Discovery Institute of Washington University, and St. Louis Children’s Hospital.

Dr. Dobbs is a Senior Editor for Clinical Orthopaedics and Related Research.

The authors report no other conflicts of interest.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

This work was performed at Washington University School of Medicine.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 219 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Buchan, J.G., Alvarado, D.M., Haller, G. et al. Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?. Clin Orthop Relat Res 472, 3216–3225 (2014). https://doi.org/10.1007/s11999-014-3766-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11999-014-3766-8

Keywords

Navigation