Skip to main content

Advertisement

SpringerLink
Log in

Child and adolescent psychiatric genetics

  • Review
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

An Erratum to this article was published on 28 April 2010

An Erratum to this article was published on 28 April 2010

Abstract

The current status of child and adolescent psychiatric genetics appears promising in light of the initiation of genome-wide association studies (GWAS) for diverse polygenic disorders and the molecular elucidation of monogenic Rett syndrome, for which recent functional studies provide hope for pharmacological treatment strategies. Within the last 50 years, tremendous progress has been made in linking genetic variation to behavioral phenotypes and psychiatric disorders. We summarize the major findings of the Human Genome Project and dwell on largely unsuccessful candidate gene and linkage studies. GWAS for the first time offer the possibility to detect single nucleotide polymorphisms and copy number variants without a priori hypotheses as to their molecular etiology. At the same time it is becoming increasingly clear that very large sample sizes are required in order to enable genome wide significant findings, thus necessitating further large-scaled ascertainment schemes for the successful elucidation of the molecular genetics of childhood and adolescent psychiatric disorders. We conclude by reflecting on different scenarios for future research into the molecular basis of early onset psychiatric disorders. This review represents the introductory article of this special issue of the European Child and Adolescent Psychiatry.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abelson JF, Kwan KY, O’Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rasin MR, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS 4th, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Sestan N, State MW (2005) Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 310:317–320

    CAS  PubMed  Google Scholar 

  2. Achenbach TM (1991) Manual for the Child Behavior Checklist/4-18 and 1991 profile. Department of Psychiatry, University of Vermont, Burlington, VT

  3. Acosta MT, Gioia GA, Silva AJ (2006) Neurofibromatosis type 1: new insights into neurocognitive issues. Curr Neurol Neurosci Rep. 6:136–143

    CAS  PubMed  Google Scholar 

  4. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23:185–188

    CAS  PubMed  Google Scholar 

  5. Armstrong DD (2002) Neuropathology of Rett syndrome. Ment Retard Dev Disabil Res Rev 8:72–76

    PubMed  Google Scholar 

  6. Attia J, Ioannidis JP, Thakkinstian A, McEvoy M, Scott RJ, Minelli C, Thompson J, Infante-Rivard C, Guyatt G (2009) How to use an article about genetic association. B: are the results of the study valid? JAMA 301:191–197

    CAS  PubMed  Google Scholar 

  7. Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, Adams MD, Myers EW, Li PW, Eichler EE (2002) Recent segmental duplications in the human genome. Science 297:1003–1007

    CAS  PubMed  Google Scholar 

  8. Ballas N, Lioy DT, Grunseich C, Mandel G (2009) Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 12:311–317

    CAS  PubMed  Google Scholar 

  9. Banaschewski T, Becker K, Scherag S, Franke B, Coghill D (2010) Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry (this issue)

  10. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nöthen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Höfels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ (2008) A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13:197–207

    CAS  PubMed  Google Scholar 

  11. Ben-Shachar S, Chahrour M, Thaller C, Shaw CA, Zoghbi YH (2009) Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum Mol Genet 18:2431–2442

    CAS  PubMed  Google Scholar 

  12. Brendel C, Klahold E, Gärtner J, Huppke P (2009) Suppression of nonsense mutations in Rett Syndrome by aminoglycoside antibiotics. Pediatr Res 65:520–523

    CAS  PubMed  Google Scholar 

  13. Brett D, Hanke J, Lehmann G, Haase S, Delbruck S, Krueger S, Reich J, Bork P (2000) EST comparison indicates 38% of human mRNAs contain possible alternative splice forms. FEBS Lett 474:83–86

    CAS  PubMed  Google Scholar 

  14. Brunner HG, Ropers HH (1995) Specification of the phenotype required for men with monoamine oxidase type A deficiency. Reply to Hebebrand and Klug 1995. Hum Genet 96:374–375

    Google Scholar 

  15. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262:578–580

    CAS  PubMed  Google Scholar 

  16. Brunner HG, Nelen MR, van Zandvoort P, Abeling NG, van Gennip AH, Wolters EC, Kuiper MA, Ropers HH, van Oost BA (1993) X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Hum Genet 52:1032–1039

    CAS  PubMed  Google Scholar 

  17. Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, Sonnenblick LI, Alvarez Retuerto AI, Imielinski M, Hadley D, Bradfield JP, Kim C, Gidaya NB, Lindquist I, Hutman T, Sigman M, Kustanovich V, Lajonchere CM, Singleton A, Kim J, Wassink TH, McMahon WM, Owley T, Sweeney JA, Coon H, Nurnberger JI, Li M, Cantor RM, Minshew NJ, Sutcliffe JS, Cook EH, Dawson G, Buxbaum JD, Grant SF, Schellenberg GD, Geschwind DH, Hakonarson H (2009) Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet 5:e1000536

    PubMed  Google Scholar 

  18. Buitelaar JK (2005) ADHD: strategies to unravel its genetic architecture. J Neural Transm Suppl 69:1–17

    PubMed  Google Scholar 

  19. Burmeister M, McInnis MG, Zöllner S (2008) Psychiatric genetics: progress amid controversy. Nat Rev Genet 9:527–540

    CAS  PubMed  Google Scholar 

  20. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854

    CAS  PubMed  Google Scholar 

  21. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    CAS  PubMed  Google Scholar 

  22. Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from neurobiology to clinic. Neuron 56:422–437

    CAS  PubMed  Google Scholar 

  23. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R (2006) The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49:341–348

    CAS  PubMed  Google Scholar 

  24. Cheung J, Estivill X, Khaja R, MacDonald JR, Lau K, Tsui LC, Scherer SW (2003) Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence. Genome Biol 4:R25

    PubMed  Google Scholar 

  25. Clifford CA, Murray RM, Fulker DW (1984) Genetic and environmental influences on obsessional traits and symptoms. Psychol Med 14:791–800

    CAS  PubMed  Google Scholar 

  26. Cloninger CR, Przybeck TR, Svrakic DM (1991) The tridemisional personality questionnaire: U.S. normative data. Psychol Repl 69:1047–1057

  27. Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, David Sweatt J, Zoghbi HY (2004) Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13:2679–2689

    CAS  PubMed  Google Scholar 

  28. Cook EH Jr, Scherer SW (2008) Copy-number variations associated with neuropsychiatric conditions. Nature 16:919–923

    Google Scholar 

  29. Costa PT, McCrae RR (1990) Personality disorders and the five-factor model of personality. J Pers Disord 4:362–371

    Google Scholar 

  30. DeBie P, Muller P, Wijmenga C, Klomp LW (2007) Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 44:673–688

    CAS  Google Scholar 

  31. Devlin B, Roeder K, Wasserman L (2003) Analysis of multilocus models of association. Genet Epidemiol 25:36–47

    CAS  PubMed  Google Scholar 

  32. Devys D, Lutz Y, Rouyer N, Bellocq JP, Mandel JL (1993) The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet 4:335–340

    CAS  PubMed  Google Scholar 

  33. Eley TC, Bolton D, O’Connor TG, Perrin S, Smith P, Plomin R (2003) A twin study of anxiety-related behaviors in pre-school children. J Child Psychol Psyc 44:945–960

    Google Scholar 

  34. Elia J, Gai X, Xie HM, Perin JC, Geiger E, Glessner JT, D’arcy M, Deberardinis R, Frackelton E, Kim C, Lantieri F, Muganga BM, Wang L, Takeda T, Rappaport EF, Grant SF, Berrettini W, Devoto M, Shaikh TH, Hakonarson H, White PS (2009) Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry (Epub ahead of print)

  35. Emes RD, Riley MC, Laukaitis CM, Goodstadt L, Karn RC, Ponting CP (2004) Comparative evolutionary genomics of androgen-binding protein genes. Genome Res 14:1516–1529

    CAS  PubMed  Google Scholar 

  36. The ENCODE Project: ENCyclopedia Of DNA Elements. http://www.genome.gov/10005107. Accessed 2 Nov 2009

  37. Eysenck HJ, Eysenck SBG, Barret P (1985) A revised version of the Psychoticism Scale. Pers Individ Dif 76:21–29

    Google Scholar 

  38. Falk CT, Rubinstein P (1987) Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations. Ann Hum Genet 51:227–233

    CAS  PubMed  Google Scholar 

  39. Farooqi IS, Bullmore E, Keogh J, Gillard J, O’Rahilly S, Fletcher PC (2007) Leptin regulates striatal regions and human eating behavior. Science 317:1355

    CAS  PubMed  Google Scholar 

  40. Fenson L, Dale PS, Reznick JS (1993) MacArthur Communicative Development Inventories. Singular Publishing Group, San Diego, CA

  41. Ferreira MA, O’Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, Fan J, Kirov G, Perlis RH, Green EK, Smoller JW, Grozeva D, Stone J, Nikolov I, Chambert K, Hamshere ML, Nimgaonkar VL, Moskvina V, Thase ME, Caesar S, Sachs GS, Franklin J, Gordon-Smith K, Ardlie KG, Gabriel SB, Fraser C, Blumenstiel B, Defelice M, Breen G, Gill M, Morris DW, Elkin A, Muir WJ, McGhee KA, Williamson R, MacIntyre DJ, MacLean AW, St CD, Robinson M, Van Beck M, Pereira AC, Kandaswamy R, McQuillin A, Collier DA, Bass NJ, Young AH, Lawrence J, Ferrier IN, Anjorin A, Farmer A, Curtis D, Scolnick EM, McGuffin P, Daly MJ, Corvin AP, Holmans PA, Blackwood DH, Gurling HM, Owen MJ, Purcell SM, Sklar P, Craddock N, Wellcome Trust Case Control Consortium (2008) Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 40:1056–1958

    CAS  PubMed  Google Scholar 

  42. Feuk L, Macdonald JR, Tang T, Carson AR, Li M, Rao G, Khaja R, Scherer SW (2005) Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genet 1:e56

    PubMed  Google Scholar 

  43. Fickett JW, Wasserman WW (2000) Discovery and modeling of transcriptional regulatory regions. Curr Opin Biotechnol 11:19–24

    CAS  PubMed  Google Scholar 

  44. Foley DL, Eaves LJ, Wormley B, Silberg JL, Maes HH, Kuhn J, Riley B (2004) Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Arch Gen Psychiatry 61:738–744

    CAS  PubMed  Google Scholar 

  45. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609

    CAS  PubMed  Google Scholar 

  46. Freitag CM, Rhode, LA, Lempp T, Romanos M (2010) Phenotypic and measurement influences on heritability estimates in childhood ADHD. Eur Child Adolesc Psychiatry (this issue)

  47. Freitag CM, Staal W, Klauck SM, Duketis E, Waltes R (2010) Genetics of autistic disorders: review and clinical implications. Eur Child Adolesc Psychiaty (this issue)

  48. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225–2229

    CAS  PubMed  Google Scholar 

  49. Garner DM, Olmsted MP, Bohr Y, Garfinkel PE (1982) The eating attitudes test: psychometric features and clinical correlates. Psychol Med 12:871–878

    Google Scholar 

  50. Garner DM, Olmsted MP, Polivy J (1983) Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia. Int J Eat Disord 2:15–34

    Google Scholar 

  51. Gelhorn HL, Stallings MC, Young SE, Corley RP, Rhee SH, Hewitt JK (2005) Genetic and environmental influences of conduct disorder: symptom, domain and full-scale analyses. J Child Psychol Psy 46:580–591

    Google Scholar 

  52. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T, Game RM, Rudd DS, Zurawiecki D, McDougle CJ, Davis LK, Miller J, Posey DJ, Michaels S, Kolevzon A, Silverman JM, Bernier R, Levy SE, Schultz RT, Dawson G, Owley T, McMahon WM, Wassink TH, Sweeney JA, Nurnberger JI, Coon H, Sutcliffe JS, Minshew NJ, Grant SF, Bucan M, Cook EH, Buxbaum JD, Devlin B, Schellenberg GD, Hakonarson H (2009) Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459:569–573

    CAS  PubMed  Google Scholar 

  53. Goetghebuer T, Ota MO, Kebbeh B, John M, Jackson-Sillah D, Vekemans J, Marchant A, Newport M, Weiss HA (2003) Delay in motor development of twins in Africa: a prospective cohort study. Twin Res 6:279–284

    PubMed  Google Scholar 

  54. Von Gontard A, Schaumburg H, Hollmann E, Eiberg H, Rittig S (2001) The genetics of enuresis: a review. J Urol 166:2438–2443

    Google Scholar 

  55. Goodstadt L, Ponting CP (2001) Sequence variation and disease in the wake of the draft human genome. Hum Mol Genet 10:2209–2214

    CAS  PubMed  Google Scholar 

  56. Grant SF (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320–323

    CAS  PubMed  Google Scholar 

  57. Gudbjartsson DF, Walters GB, Thorleifsson G, Stefansson H, Halldorsson BV, Zusmanovich P, Sulem P, Thorlacius S, Gylfason A, Steinberg S, Helgadottir A, Ingason A, Steinthorsdottir V, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Pedersen O, Aben KK, Witjes JA, Swinkels DW, den Heijer M, Franke B, Verbeek AL, Becker DM, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Gulcher J, Kiemeney LA, Kong A, Thorsteinsdottir U, Stefansson K (2008) Many sequence variants affecting diversity of adult human height. Nat Genet 40:609–615

    CAS  PubMed  Google Scholar 

  58. Hagberg B, Aicardi J, Dias K, Ramos O (1983) A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol 14:471–479

    CAS  PubMed  Google Scholar 

  59. Hardy J, Singleton A (2009) Genomewide association studies and human disease. New Engl J Med 360:1759–1768

    CAS  PubMed  Google Scholar 

  60. Harrison PM, Kumar A, Lang N, Snyder M, Gerstein M (2002) A question of size: the eukaryotic proteome and the problems in defining it. Nucleic Acids Res 30:1083–1090

    CAS  PubMed  Google Scholar 

  61. Hashimoto K, Koizumi H, Nakazato M, Shimizu E, Iyo M (2005) Role of brain-derived neurotrophic factor in eating disorders: recent findings and its pathophysiological implications. Prog Neuropsychopharmacol Biol Psychiatry 29:499–504

    CAS  PubMed  Google Scholar 

  62. Hebebrand J, Propping P (1990) Genetic aspects of brain maturation and behavior. In: Rothenberger A (ed) Brain and behavior in child psychiatry. Springer, Berlin, pp 79–105

    Google Scholar 

  63. Hebebrand J, Klug B (1995) Specification of the phenotype required for men with monoamine oxidase type A deficiency. Hum Genet 96:372–376

    CAS  PubMed  Google Scholar 

  64. Heiser P, Friedel S, Dempfle A, Konrad K, Smidt J, Grabarkiewicz J, Herpertz-Dahlmann B, Remschmidt H, Hebebrand J (2004) Molecular genetic aspects of attention-deficit/hyperactivity disorder. Neurosci Biobehav R 28:625–641

    CAS  Google Scholar 

  65. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106(23):9362–9367

    CAS  PubMed  Google Scholar 

  66. Hindorff LA, Junkins HA, Mehta JP, Manolio TA. A catalog of published genome-wide association studies. http://www.genome.gov/26525384. Accessed 2 Nov 2009

  67. Hinney A, Hebebrand J (2008) Polygenic obesity in humans. Obes Facts 1:35–42

    CAS  PubMed  Google Scholar 

  68. Hinney A, Vogel CI, Hebebrand J (2010) From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry (this issue)

  69. Hirschhorn JN, Lettre G (2009) Progress in genome-wide association studies of human height. Horm Res 71(S2):5–131

    CAS  PubMed  Google Scholar 

  70. Hite KC, Adams VH, Hansen JC (2009) Recent advances in MeCP2 structure and function. Biochem Cell Biol 87:219–227

    CAS  PubMed  Google Scholar 

  71. Hudziak JJ, Van Beijsterveldt CE, Althoff RR, Stanger C, Rettew DC, Nelson EC, Todd RD, Bartels M, Boomsma DI (2004) Genetic and environmental contributions to the child behavior checklist obsessive–compulsive scale: a cross-cultural twin study. Arch Gen Psychiatry 61:608–616

    PubMed  Google Scholar 

  72. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    CAS  PubMed  Google Scholar 

  73. Van Hulle CA, Goldsmith HH, Lemery KS (2004) Genetic, environmental, and gender effects on individual differences in toddler expressive language. J Speech Lang Hear Res 47:904–912

    PubMed  Google Scholar 

  74. Human Epigenome Project. http://www.epigenome.org/. Accessed 2 Nov 2009

  75. Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983

    Google Scholar 

  76. Iles MM (2008) What can genome-wide association studies tell us about the genetics of common disease? PLoS Genet 4:e33

    PubMed  Google Scholar 

  77. International HapMap Project. http://www.hapmap.org/index.html.en. Accessed 2 Nov 2009

  78. International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Google Scholar 

  79. International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931–945

    Google Scholar 

  80. International Schizophrenia Consortium, Purcell SM, Wray NR, Stone JL, Visscher PM, O’Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748–752

    CAS  PubMed  Google Scholar 

  81. International SNP Map Working Group (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–933

    Google Scholar 

  82. Jang KL, Livesley WJ, Vernon PA (1996) Heritability of the big five personality dimensions and their facets: a twin study. J Pers 64:577–591

    CAS  PubMed  Google Scholar 

  83. Jinnah HA (2009) Lesch-Nyhan disease: from mechanism to model and back again. Dis Models Mech 2:116–121

    CAS  Google Scholar 

  84. Kazantsev AG, Thompson LM (2008) Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 7:854–868

    CAS  PubMed  Google Scholar 

  85. Keller MC, Coventry WL, Heath AC, Martin NG (2005) Widespread evidence for non-additive genetic variation in Cloninger’s and Eysenck’s personality dimensions using a twin plus sibling design. Behav Genet 35:707–721

    PubMed  Google Scholar 

  86. Kendler KS (2005) “A gene for”: the nature of gene action in psychiatric disorders. Am J Psychiat 162:1243–1252

    PubMed  Google Scholar 

  87. Khoury MJ, Bertram L, Boffetta P, Butterworth AS, Chanock SJ, Dolan SM, Fortier I, Garcia-Closas M, Gwinn M, Higgins JP, Janssens AC, Ostell J, Owen RP, Pagon RA, Rebbeck TR, Rothman N, Bernstein JL, Burton PR, Campbell H, Chockalingam A, Furberg H, Little J, O’Brien TR, Seminara D, Vineis P, Winn DM, Yu W, Ioannidis JP (2009) Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases. Am J Epidemiol 170:269–279

    PubMed  Google Scholar 

  88. Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, Hansen N, Teague B, Alkan C, Antonacci F, Haugen E, Zerr T, Yamada NA, Tsang P, Newman TL, Tüzün E, Cheng Z, Ebling HM, Tusneem N, David R, Gillett W, Phelps KA, Weaver M, Saranga D, Brand A, Tao W, Gustafson E, McKernan K, Chen L, Malig M, Smith JD, Korn JM, McCarroll SA, Altshuler DA, Peiffer DA, Dorschner M, Stamatoyannopoulos J, Schwartz D, Nickerson DA, Mullikin JC, Wilson RK, Bruhn L, Olson MV, Kaul R, Smith DR, Eichler EE (2008) Mapping and sequencing of structural variation from eight human genomes. Nature 453:56–64

    CAS  PubMed  Google Scholar 

  89. Kupper LL, Palmer LJ (2002) Matching. In: Elston RC, Olson J, Palmer LJ (eds) Biostatistical genetics and genetic epidemiology. Wiley, Chichester, pp 518–523

    Google Scholar 

  90. Lander E, Schork N (1994) Genetic dissection of complex traits. Science 265:2037–2048

    CAS  PubMed  Google Scholar 

  91. Leckman JF, Vaccarino FM, Lambroso PJ (2007) From genes to brain: developmental neurobiology. In: Martin A, Volkmar FR (eds) Lewis’s child and adolescent psychiatry. Lippincott Williams & Wilkins, Philadelphia, pp 177–188

    Google Scholar 

  92. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176

    CAS  PubMed  Google Scholar 

  93. Lejeune J, Gautier M, Turpin R (1959) Étude des chromosomes somatiques de neuf enfants mongoliens. C R Hebd Seances Acad Sci 248:1721–1722

    CAS  PubMed  Google Scholar 

  94. Lejeune J, Lafourcade J, Berger R, Vialatte J, Boeswillwald M, Seringe P, Tuppin R (1963) 3 cases of partial deletion of the short arm of a 5 chromosome. C R Hebd Seances Acad Sci 257:3098–3102

    CAS  PubMed  Google Scholar 

  95. Lencz T, Morgan TV, Athanasiou M, Dain B, Reed CR, Kane JM, Kucherlapati R, Malhotra AK (2007) Converging evidence for a pseudoautosomal cytokine receptor gene locus in Schizophrenia. Mol Psychiatry 12:572–580

    CAS  PubMed  Google Scholar 

  96. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G, Lin Y, MacDonald JR, Pang AW, Shago M, Stockwell TB, Tsiamouri A, Bafna V, Bansal V, Kravitz SA, Busam DA, Beeson KY, McIntosh TC, Remington KA, Abril JF, Gill J, Borman J, Rogers YH, Frazier ME, Scherer SW, Strausberg RL, Venter JC (2007) The diploid genome sequence of an individual human. PLoS Biol 5:e254

    PubMed  Google Scholar 

  97. Lewis JC, Thomas HV, Murphy KC, Sampson JR (2004) Genotype and psychological phenotype in tuberous sclerosis. J Med Genet 41:203–207

    CAS  PubMed  Google Scholar 

  98. Li H, Yamagata T, Mori M, Yasuhara A, Momoi MY (2005) Mutation analysis of methyl-CpG binding protein family genes in autistic patients. Brain Dev 27:321–325

    CAS  PubMed  Google Scholar 

  99. Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, Scheet P, Gwinn M, Williamson RE, Zou GY, Hutchings K, Johnson CY, Tait V, Wiens M, Golding J, van Duijn C, McLaughlin J, Paterson A, Wells G, Fortier I, Freedman M, Zecevic M, King R, Infante-Rivard C, Stewart A, Birkett N (2009) Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement. Eur J Epidemiol 24:37–55

    PubMed  Google Scholar 

  100. Loat CS, Curran S, Lewis CM, Duvall J, Geschwind D, Bolton P, Craig IW (2008) Methyl-CpG-binding protein 2 polymorphisms and vulnerability to autism. Genes Brain Behav 7:754–760

    CAS  PubMed  Google Scholar 

  101. Luikenhuis S, Giacometti E, Beard CF, Jaenisch R (2004) Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci USA 101:6033–6038

    CAS  PubMed  Google Scholar 

  102. Maezawa I, Swanberg SD, Harvey D, LaSalle JM, Jin LW (2009) Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 29:505150–505161

    Google Scholar 

  103. Manolio TA, Brooks LD, Collins FS (2008) A HapMap harvest of insights into the genetics of common disease. J Clin Invest 118:1590–1605

    CAS  PubMed  Google Scholar 

  104. Margallo-Lana M, Morris CM, Gibson AM, Tan AL, Kay DW, Tyrer SP, Moore BP, Ballard CG (2004) Influence of the amyloid precursor protein locus on dementia in Down syndrome. Neurology 62:1996–1998

    CAS  PubMed  Google Scholar 

  105. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, MS, Chen YJ, Chen Z, Dewell SB, Du L, Fierro JM, Gomes XV, Godwin BC, He W, Helgesen S, Ho CH, Irzyk GP, Jando SC, Alenquer ML, Jarvie TP, Jirage KB, Kim JB, Knight JR, Lanza JR, Leamon JH, Lefkowitz SM, Lei M, Li J, Lohman KL, Lu H, Makhijani VB, McDade KE, McKenna MP, Myers EW, Nickerson E, Nobile JR, Plant R, Puc BP, Ronan MT, Roth GT, Sarkis GJ, Simons JF, Simpson JW, Srinivasan M, Tartaro KR, Tomasz A, Vogt KA, Volkmer GA, Wang SH, Wang Y, Weiner MP, Yu P, Begley RF, Rothberg JM (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376–380

  106. McGrath LM, Smith SD, Pennington BF (2006) Breakthroughs in the search for dyslexia candidate genes. Trends Mol Med 12:333–1341

    CAS  PubMed  Google Scholar 

  107. McMullan DJ, Bonin M, Hehir-Kwa JY, de Vries BB, Dufke A, Rattenberry E, Steehouwer M, Moruz L, Pfundt R, de Leeuw N, Riess A, Altug-Teber O, Enders H, Singer S, Grasshoff U, Walter M, Walker JM, Lamb CV, Davison EV, Brueton L, Riess O, Veltman JA (2009) Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: a multicenter study. Hum Mutat 30:1082–1092

    CAS  PubMed  Google Scholar 

  108. Mehan MR, Freimer NB, Ophoff RA (2004) A genome-wide survey of segmental duplications that mediate common human genetic variation of chromosomal architecture. Hum Genomics 1:335–344

    CAS  PubMed  Google Scholar 

  109. Meyer HE (2009) HUPO Brain Proteome Project. http://www.hbpp.org/5602.html. Accessed 2 Nov 2009

  110. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71

    CAS  PubMed  Google Scholar 

  111. Mironov AA, Fickett JW, Gelfand MS (1999) Frequent alternative splicing of human genes. Genome Res 9:1288–1293

    CAS  PubMed  Google Scholar 

  112. Modrek B, Lee C (2002) A genomic view of alternative splicing. Nat Genet 30:13–19

    CAS  PubMed  Google Scholar 

  113. Moretti P, Bouwknecht JA, Teague R, Paylor R, Zoghbi HY (2005) Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum Mol Genet 14:205–220

    CAS  PubMed  Google Scholar 

  114. Morton NE (1998) Significance levels in complex inheritance. Am J Hum Genet 62:690–697

    CAS  PubMed  Google Scholar 

  115. Mouse Genome Sequencing Consortium (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562

    Google Scholar 

  116. Nahon JL (2003) Birth of ‘human-specific’ genes during primate evolution. Genetica 118:193–208

    CAS  PubMed  Google Scholar 

  117. National Research Council (1988) Mapping and sequencing the human genome. National Academy Press, Washington, DC. http://www.hugo-international.org/

  118. O’Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L, Dwyer S, Holmans P, Marchini JL, Spencer CC, Howie B, Leung HT, Hartmann AM, Möller HJ, Morris DW, Shi Y, Feng G, Hoffmann P, Propping P, Vasilescu C, Maier W, Rietschel M, Zammit S, Schumacher J, Quinn EM, Schulze TG, Williams NM, Giegling I, Iwata N, Ikeda M, Darvasi A, Shifman S, He L, Duan J, Sanders AR, Levinson DF, Gejman PV, Cichon S, Nöthen MM, Gill M, Corvin A, Rujescu D, Kirov G, Owen MJ, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Cloninger CR, Molecular Genetics of Schizophrenia Collaboration (2008) Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 40:1053–1055

    PubMed  Google Scholar 

  119. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez G, Cho JH (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    CAS  PubMed  Google Scholar 

  120. Ong KK, Elks CE, Li S, Zhao JH, Luan J, Andersen LB, Bingham SA, Brage S, Smith GD, Ekelund U, Gillson CJ, Glaser B, Golding J, Hardy R, Khaw KT, Kuh D, Luben R, Marcus M, McGeehin MA, Ness AR, Northstone K, Ring SM, Rubin C, Sims MA, Song K, Strachan DP, Vollenweider P, Waeber G, Waterworth DM, Wong A, Deloukas P, Barroso I, Mooser V, Loos RJ, Wareham NJ (2009) Genetic variation in LIN28B is associated with the timing of puberty. Nat Genet May 17 [Epub ahead of print]

  121. Pavlicek A, Noskov VN, Kouprina N, Barrett JC, Jurka J, Larionov V (2004) Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. Hum Mol Genet 13:2737–2751

    CAS  PubMed  Google Scholar 

  122. Pennisi E (2007) Breakthrough of the year. Human genetic variation. Science 318:1842–1843

    CAS  PubMed  Google Scholar 

  123. Peter I, Vainder M, Livshits G (1999) Genetic analysis of motor milestones attainment in early childhood. Twin Res 2:1–9

    CAS  PubMed  Google Scholar 

  124. Plomin R (2005) Finding genes in child psychology and psychiatry: when are we going to be there? J Child Psychol Psychiatry 46:1030–1038

    PubMed  Google Scholar 

  125. Plomin R, Daniels D (1987) Why are children in the same family so different from each other? Behav Brain Sci 10:1–16

    Google Scholar 

  126. Pritchard JK, Rosenberg NA (1999) Use of unlinked genetic markers to detect population stratification in association studies. Am J Hum Genet 65:220–228

    CAS  PubMed  Google Scholar 

  127. Reichwald K, Thiesen J, Wiehe T, Weitzel J, Stratling WH, Kioschis P, Poustka A, Rosenthal A, Platzer M (2000) Comparative sequence analysis of the MECP2-locus in human and mouse reveals new transcribed regions. Mamm Genome 11:182–190

    CAS  PubMed  Google Scholar 

  128. Rett A (1966) On a unusual brain atrophy syndrome in hyperammonemia in childhood. Wien Med Wochenschr 116:723–726

    CAS  PubMed  Google Scholar 

  129. Risch NJ (2000) Searching for genetic determinants in the new millennium. Nature 405:847–856

    CAS  PubMed  Google Scholar 

  130. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517

    CAS  PubMed  Google Scholar 

  131. Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301:2462–2471

    CAS  PubMed  Google Scholar 

  132. Roest Crollius H, Jaillon O, Bernot A, Dasilva C, Bouneau L, Fischer C, Fizames C, Wincker P, Brottier P, Quetier F, Saurin W, Weissenbach J (2000) Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence. Nat Genet 25:235–238

    CAS  PubMed  Google Scholar 

  133. Rommelse N, Franke B, Geurts HM, Hartman CS, Buitelaar JK (2010) Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder: a review. Eur Child Adolesc Psychiatry (this issue)

  134. Rutherford J, McGuffin P, Katz RJ, Murray RM (1993) Genetic influences on eating attitudes in a normal female twin pair population. Psychol Med 23:425–436

    CAS  PubMed  Google Scholar 

  135. Sabeti PC, Reich DE, Higgins JM, Levine HZ, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D, Cooper R, Kwiatkowski D, Ward R, Lander ES (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419:832–827

    Google Scholar 

  136. Samaco RC, Nagarajan RP, Braunschweig D, LaSalle JM (2004) Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Hum Mol Genet 13:629–639

    CAS  PubMed  Google Scholar 

  137. Samaco RC, Hogart A, LaSalle JM (2005) Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14:483–492

    CAS  PubMed  Google Scholar 

  138. Samaco RC, Fryer JD, Ren J, Fyffe S, Chao HT, Sun Y, Greer JJ, Zoghbi HY, Neul JL (2008) A partial loss of function allele of methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome. Hum Mol Genet 17:1718–1727

    CAS  PubMed  Google Scholar 

  139. Santangelo SL, Tsatsanis K (2005) What is known about autism: genes, brain, and behaviour. Am J Pharmacogenomics 5:71–92

    CAS  PubMed  Google Scholar 

  140. Saunders CL, Chiodini BD, Sham P, Lewis CM, Abkevich V, Adeyemo AA, de Andrade M, Arya R, Berenson GS, Blangero J, Boehnke M, Borecki IB, Chagnon YC, Chen W, Comuzzie AG, Deng HW, Duggirala R, Feitosa MF, Froguel P, Hanson RL, Hebebrand J, Huezo-Dias P, Kissebah AH, Li W, Luke A, Martin LJ, Nash M, Ohman M, Palmer LJ, Peltonen L, Perola M, Price RA, Redline S, Srinivasan SR, Stern MP, Stone S, Stringham H, Turner S, Wijmenga C, Collier DA (2007) Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity 15:2263–2275

    PubMed  Google Scholar 

  141. Scherag S, Hebebrand J, Hinney A (2010) Eating disorders: the current status of molecular genetic research. Eur Child Adolesc Psychiatry (this issue)

  142. Schormair B, Kemlink D, Roeske D, Eckstein G, Xiong L, Lichtner P, Ripke S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Högl B, Frauscher B, Gschliesser V, Poewe W, Peglau I, Vodicka P, Vávrová J, Sonka K, Nevsimalova S, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T, Winkelmann J (2008) PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet 40:946–948

    CAS  PubMed  Google Scholar 

  143. Schulte-Körne G, Scerri TS (2010) Genetics of developmental dyslexia. Eur Child Adolesc Psychiatry (this issue)

  144. Scriver CR (2007) The PAH gene, phenylketonuria, and a paradigm shift. Hum Mutat 28:831–845

    CAS  PubMed  Google Scholar 

  145. Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, Månér S, Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K, Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M (2004) Large-scale copy number polymorphism in the human genome. Science 305:525–528

    CAS  PubMed  Google Scholar 

  146. Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY (2002) Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 11:115–124

    CAS  PubMed  Google Scholar 

  147. Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe’er I, Dudbridge F, Holmans PA, Whittemore AS, Mowry BJ, Olincy A, Amin F, Cloninger CR, Silverman JM, Buccola NG, Byerley WF, Black DW, Crowe RR, Oksenberg JR, Mirel DB, Kendler KS, Freedman R, Gejman PV (2009) Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460:753–757

    CAS  PubMed  Google Scholar 

  148. Single Nucleotide Polymorphism. RELEASE: NCBI dbSNP Build 130. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_summary.cgi. Accessed 2 Nov 2009

  149. Smoller JW, Finn CT (2003) Family, twin, and adoption studies of bipolar disorder. Am J Med Genet C Semin Med Genet 123C:48–58

    PubMed  Google Scholar 

  150. Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52:506–516

    CAS  PubMed  Google Scholar 

  151. Stamm S (2002) Signals and their transduction pathways regulating alternative splicing: a new dimension of the human genome. Hum Mol Genet 11:2409–2416

    CAS  PubMed  Google Scholar 

  152. Stefansson H, Rye DB, Hicks A, Petursson H, Ingason A, Thorgeirsson TE, Palsson S, Sigmundsson T, Sigurdsson AP, Eiriksdottir I, Soebech E, Bliwise D, Beck JM, Rosen A, Waddy S, Trotti LM, Iranzo A, Thambisetty M, Hardarson GA, Kristjansson K, Gudmundsson LJ, Thorsteinsdottir U, Kong A, Gulcher JR, Gudbjartsson D, Stefansson K (2007) A genetic risk factor for periodic limb movements in sleep. New Engl J Med 357:639–647

    CAS  PubMed  Google Scholar 

  153. Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, GROUP, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455:232–236

    CAS  PubMed  Google Scholar 

  154. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, Werge T, Pietiläinen OP, Mors O, Mortensen PB, Sigurdsson E, Gustafsson O, Nyegaard M, Tuulio-Henriksson A, Ingason A, Hansen T, Suvisaari J, Lonnqvist J, Paunio T, Børglum AD, Hartmann A, Fink-Jensen A, Nordentoft M, Hougaard D, Norgaard-Pedersen B, Böttcher Y, Olesen J, Breuer R, Möller HJ, Giegling I, Rasmussen HB, Timm S, Mattheisen M, Bitter I, Réthelyi JM, Magnusdottir BB, Sigmundsson T, Olason P, Masson G, Gulcher JR, Haraldsson M, Fossdal R, Thorgeirsson TE, Thorsteinsdottir U, Ruggeri M, Tosato S, Franke B, Strengman E, Kiemeney LA, Genetic Risk Outcome in Psychosis (GROUP), Melle I, Djurovic S, Abramova L, Kaleda V, Sanjuan J, de Frutos R, Bramon E, Vassos E, Fraser G, Ettinger U, Picchioni M, Walker N, Toulopoulou T, Need AC, Ge D, Yoon JL, Shianna KV, Freimer NB, Cantor RM, Murray R, Kong A, Golimbet V, Carracedo A, Arango C, Costas J, Jönsson EG, Terenius L, Agartz I, Petursson H, Nöthen MM, Rietschel M, Matthews PM, Muglia P, Peltonen L, St Clair D, Goldstein DB, Stefansson K, Collier DA (2009) Common variants conferring risk of schizophrenia. Nature 460:744–747

    CAS  PubMed  Google Scholar 

  155. Steinle NI, Hsueh WC, Snitker S, Pollin TI, Sakul H, StJean PL, Bell CJ, Mitchell BD, Shuldiner AR (2002) Eating behavior in the old order Amish: heritability analysis and a genome-wide linkage analysis. Am J Clin Nutr 75:1098–1106

    CAS  PubMed  Google Scholar 

  156. Stolberg S (1993) Scientists discover gene linked to aggressive behavior in humans. The Tech 113. http://tech.mit.edu/V113/N51/agression.51w.html. Accessed 2 Nov 2009

  157. Stunkard AJ, Messick S (1985) The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res 29:71–83

    Google Scholar 

  158. Sulem P, Gudbjartsson DF, Rafnar T, Holm H, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Alexandersen P, Feenstra B, Boyd HA, Aben KK, Verbeek AL, Roeleveld N, Jonasdottir A, Styrkarsdottir U, Steinthorsdottir V, Karason A, Stacey SN, Gudmundsson J, Jakobsdottir M, Thorleifsson G, Hardarson G, Gulcher J, Kong A, Kiemeney LA, Melbye M, Christiansen C, Tryggvadottir L, Thorsteinsdottir U, Stefansson K (2009) Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche. Nat Genet May 17 [Epub ahead of print]

  159. Sullivan PF, Neale MC, Kendler KS (2000) Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 157:1552–1562

    CAS  PubMed  Google Scholar 

  160. Sullivan PF, Kendler KS, Neale MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 60:1187–1192

    PubMed  Google Scholar 

  161. Terwilliger J, Ott J (1992) A haplotype-based ‘haplotype relative risk’ approach to detecting allelic associations. Hum Hered 42:337–346

    CAS  PubMed  Google Scholar 

  162. 1000 Genomes Project Data Release. http://www.1000genomes.org/page.php. Accessed 2 Nov 2009

  163. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M (2009) Partial reversal of Rett syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci USA. 106(6):2029–2034

    CAS  PubMed  Google Scholar 

  164. Tsuang DW, Faraone SV (2001) Tsuang MT genetic counseling for psychiatric disorders. Curr Psychiatry Rep 3:138–143

    CAS  PubMed  Google Scholar 

  165. Urdinguio RG, Lopez-Serra L, Lopez-Nieva P, Alaminos M, Diaz-Uriarte R, Fernandez AF, Esteller M (2008) Mecp2-null mice provide new neuronal targets for Rett syndrome. PLoS One 3:e3669

    PubMed  Google Scholar 

  166. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J et al (2001) The sequence of the human genome. Science 291:1304–1351

    CAS  PubMed  Google Scholar 

  167. Walitza S, Wendland JR, Gruenblatt E, Warnke A, Sontag TA, Tucha O, Lange KW (2010) Genetics of early-onset obsessive-compulsive disorder. Eur Child Adolesc Psychiatry (this issue)

  168. Walker FO (2007) Huntington’s disease. Lancet 369:218–228

    CAS  PubMed  Google Scholar 

  169. Wang J, Wang W, Li R, Li Y, Tian G, Goodman L, Fan W, Zhang J, Li J, Zhang J, Guo Y, Feng B, Li H, Lu Y, Fang X, Liang H, Du Z, Li D, Zhao Y, Hu Y, Yang Z, Zheng H, Hellmann I, Inouye M, Pool J, Yi X, Zhao J, Duan J, Zhou Y, Qin J, Ma L, Li G, Yang Z, Zhang G, Yang B, Yu C, Liang F et al (2008) The diploid genome sequence of an Asian individual. Nature 456:60–65

    CAS  PubMed  Google Scholar 

  170. Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A, Owley T, Sweeney JA, Brune CW, Cantor RM, Bernier R, Gilbert JR, Cuccaro ML, McMahon WM, Miller J, State MW, Wassink TH, Coon H, Levy SE, Schultz RT, Nurnberger JI, Haines JL, Sutcliffe JS, Cook EH, Minshew NJ, Buxbaum JD, Dawson G, Grant SF, Geschwind DH, Pericak-Vance MA, Schellenberg GD, Hakonarson H (2009) Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 459:528–533

    CAS  PubMed  Google Scholar 

  171. Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171:737–738

    CAS  PubMed  Google Scholar 

  172. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, Saemundsen E, Stefansson H, Ferreira MA, Green T, Platt OS, Ruderfer DM, Walsh CA, Altshuler D, Chakravarti A, Tanzi RE, Stefansson K, Santangelo SL, Gusella JF, Sklar P, Wu BL, Daly MJ (2008) Autism consortium. Association between microdeletion and microduplication at 16p11.2 and autism. New Engl J Med 358:667–675

    CAS  PubMed  Google Scholar 

  173. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678

    Google Scholar 

  174. Wermter AK, Laucht M, Schimmelmann B, Banaschewski T, Sonuga-Barke E, Rietschel M, Becker K (2010) From nature versus nurture to nature and nurture: gene × environment interactions in mental disorder—a selective review. Eur Child Adolesc Psychiatry (this issue)

  175. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP, Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD, Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM, Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D, Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB, Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P et al (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41:25–34

    CAS  PubMed  Google Scholar 

  176. Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T (2007) Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39:1000–1006

    CAS  PubMed  Google Scholar 

  177. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792

    CAS  PubMed  Google Scholar 

  178. Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP, Thatcher KN, Farnham PJ, Lasalle JM (2007) Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci USA 104:19416–19421

    CAS  PubMed  Google Scholar 

  179. Zhou K, Dempfle A, Arcos-Burgos M, Bakker SC, Banaschewski T, Biederman J, Buitelaar J, Castellanos FX, Doyle A, Ebstein RP, Ekholm J, Forabosco P, Franke B, Freitag C, Friedel S, Gill M, Hebebrand J, Hinney A, Jacob C, Lesch KP, Loo SK, Lopera F, McCracken JT, McGough JJ, Meyer J, Mick E, Miranda A, Muenke M, Mulas F, Nelson SF, Nguyen TT, Oades RD, Ogdie MN, Palacio JD, Pineda D, Reif A, Renner TJ, Roeyers H, Romanos M, Rothenberger A, Schäfer H, Sergeant J, Sinke RJ, Smalley SL, Sonuga-Barke E, Steinhausen HC, van der Meulen E, Walitza S, Warnke A, Lewis CM, Faraone SV, Asherson P (2008) Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 147B:1392–1398

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Bundesministerium für Bildung und Forschung (NGFNplus 01GS0820) and the Deutsche Forschungsgemeinschaft (HE144/9-1). The authors wish to thank Dr. Carla Vogel for her contribution to the paper.

Author information

Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, LVR-Klinikum Essen, University of Duisburg-Essen, Virchowstr. 174, 45147, Essen, Germany

    Johannes Hebebrand & Anke Hinney

  2. Institute of Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany

    Andre Scherag

  3. University Hospital Child and Adolescent Psychiatry, University of Bern, Bern, Switzerland

    Benno G. Schimmelmann

Authors
  1. Johannes Hebebrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Scherag
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benno G. Schimmelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anke Hinney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johannes Hebebrand.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00787-010-0108-6

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hebebrand, J., Scherag, A., Schimmelmann, B.G. et al. Child and adolescent psychiatric genetics. Eur Child Adolesc Psychiatry 19, 259–279 (2010). https://doi.org/10.1007/s00787-010-0091-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-010-0091-y

Keywords

Search

Navigation