Genome-wide analysis of attention deficit hyperactivity disorder in Norway

PLoS ONE

Volumn 10, Issue 4, 2015, Pages

  Zayats, Tetyana ^a   Athanasiu, Lavinia ^b   Sonderby, Ida ^b   Djurovic, Srdjan ^a,c   Westlye, Lars T ^b   Tamnes, Christian K ^b   Fladby, Tormod ^b,d   Aase, Heidi ^e   Zeiner, Pål ^c   Reichborn Kjennerud, Ted ^b,e   Knappskog, Per M ^a,f   Knudsen, Gun Peggy ^e   Andreassen, Ole A ^b   Johansson, Stefan ^a,f   Haavik, Jan ^a,f  

^a UNIVERSITY OF BERGEN   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

^c OSLO UNIVERSITY HOSPITAL   (Norway)

^d AKERSHUS UNIVERSITY HOSPITAL   (Norway)

^e NORWEGIAN INSTITUTE OF PUBLIC HEALTH   (Norway)

^f HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; ARTICLE; ATTENTION DEFICIT DISORDER; CELL ADHESION; CONTROLLED STUDY; DISEASE ACTIVITY; ETHNICITY; FEMALE; FOLLOW UP; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE IDENTIFICATION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENOME ANALYSIS; GENOTYPING TECHNIQUE; HUMAN; INFLAMMATION; MALE; MICROARRAY ANALYSIS; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; NORWAY; OUTCOME ASSESSMENT; PROTEIN PROTEIN INTERACTION; QUANTITATIVE TRAIT LOCUS; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SLC9A9 GENE; TPH2 GENE; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; META ANALYSIS; PATHOLOGY; PHENOTYPE;

SLC9A9 PROTEIN, HUMAN; SODIUM PROTON EXCHANGE PROTEIN; TPH2 PROTEIN, HUMAN; TRYPTOPHAN HYDROXYLASE;

ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; SODIUM-HYDROGEN ANTIPORTER; TRYPTOPHAN HYDROXYLASE;

EID: 84929459126     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0122501     Document Type: Article

References (84)

1. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1; 57(11):1313-23. PMID: 15950004
2. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007 Jun; 164(6):942-8. PMID: 17541055
3. Harpin VA. The effect of ADHD on the life of an individual, their family, and community from preschool to adult life. Arch Dis Child. 2005 Feb; 90 Suppl 1:i2-7. PMID: 15665153
4. Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry. 1993 Jul; 50 (7):565-76. PMID: 8317950
5. Weiss G, Hechtman L. Hyperactive Children Grown Up: ADHD in Children, Adolescents, and Adults. New York: Guilford Press; 1993.
6. Matza LS, Paramore C, Prasad M. A review of the economic burden of ADHD. Cost Eff Resour Alloc. 2005 Jun 9; 3:5. PMID: 15946385
7. Faraone SV, Biederman J. What is the prevalence of adult ADHD? Results of a population screen of 966 adults. J Atten Disord. 2005 Nov; 9(2):384-91. PMID: 16371661
8. Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006 Apr; 163(4):716-23. PMID: 16585449
9. Halmoy A, Fasmer OB, Gillberg C, Haavik J. Occupational outcome in adult ADHD: impact of symptom profile, comorbid psychiatric problems, and treatment: a cross-sectional study of 414 clinically diagnosed adult ADHD patients. J Atten Disord. 2009 Sep; 13(2):175-87. doi: 10.1177/1087054708329777 PMID: 19372500
10. Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin North Am. 2010 Mar; 33(1):159-80. doi: 10.1016/j.psc.2009.12.004 PMID: 20159345
11. Freitag CM, Rohde LA, Lempp T, Romanos M. Phenotypic and measurement influences on heritability estimates in childhood ADHD. Eur Child Adolesc Psychiatry. 2010 Mar; 19(3):311-23. doi: 10.1007/s00787-010-0097-5 PMID: 20213230
12. Kebir O, Tabbane K, Sengupta S, Joober R. Candidate genes and neuropsychological phenotypes in children with ADHD: review of association studies. J Psychiatry Neurosci. 2009 Mar; 34(2):88-101. PMID: 19270759
13. Franke B, Neale BM, Faraone SV. Genome-wide association studies in ADHD. Hum Genet. 2009 Jul; 126(1):13-50. doi: 10.1007/s00439-009-0663-4 PMID: 19384554
14. Gizer IR, Ficks C, Waldman ID. Candidate gene studies of ADHD: a meta-analytic review. Hum Genet. 2009 Jul; 126(1):51-90. doi: 10.1007/s00439-009-0694-x PMID: 19506906
15. Johansson S, Halleland H, Halmoy A, Jacobsen KK, Landaas ET, Dramsdahl M, et al. Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5; 147B(8):1470-5. PMID: 18081165
16. Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Roser C, Nguyen TT, et al. Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm. 2008 Nov; 115(11):1573-85. doi: 10.1007/s00702-008-0119-3 PMID: 18839057
17. Neale BM, Lasky-Su J, Anney R, Franke B, Zhou K, Maller JB, et al. Genome-wide association scan of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5; 147B (8):1337-44. doi: 10.1002/ajmg.b.30866 PMID: 18980221
18. Lasky-Su J, Anney RJ, Neale BM, Franke B, Zhou K, Maller JB, et al. Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5; 147B(8):1355-8. doi: 10.1002/ajmg.b.30869 PMID: 18937294
19. Lasky-Su J, Neale BM, Franke B, Anney RJ, Zhou K, Maller JB, et al. Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5; 147B(8):1345-54. doi: 10.1002/ajmg.b.30867 PMID: 18821565
20. Ashmore K, Cheng F. Genome-wide association studies on attention deficit hyperactivity disorder. Clinical and Experimental Pharmacology. 2013; 3(1):119.
21. Neale BM, Medland SE, Ripke S, Asherson P, Franke B, Lesch KP, et al. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010 Sep; 49(9):884-97. doi: 10.1016/j.jaac.2010.06.008 PMID: 20732625
22. Hinney A, Scherag A, Jarick I, Albayrak O, Putter C, Pechlivanis S, et al. Genome-wide association study in German patients with attention deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2011 Dec; 156B(8):888-97. doi: 10.1002/ajmg.b.31246 PMID: 22012869
23. Mick E, Todorov A, Smalley S, Hu X, Loo S, Todd RD, et al. Family-based genome-wide association scan of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010 Sep; 49 (9):898-905 e3. doi: 10.1016/j.jaac.2010.02.014 PMID: 20732626
24. Stergiakouli E, Hamshere M, Holmans P, Langley K, Zaharieva I, Hawi Z, et al. Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. Am J Psychiatry. 2012 Feb; 169(2):186-94. PMID: 22420046
25. Poelmans G, Pauls DL, Buitelaar JK, Franke B. Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am J Psychiatry. 2011 Apr; 168(4):365-77. doi: 10.1176/appi.ajp.2010.10070948 PMID: 21324949
26. Williams NM, Franke B, Mick E, Anney RJ, Freitag CM, Gill M, et al. Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. Am J Psychiatry. 2012 Feb; 169(2):195-204. PMID: 22420048
27. Addamo PK, Farrow M, Hoy KE, Bradshaw JL, Georgiou-Karistianis N. The effects of age and attention on motor overflow production - A review. Brain Res Rev. 2007 Apr; 54(1):189-204. PMID: 17300842
28. Rommelse NN, Altink ME, Arias-Vasquez A, Buschgens CJ, Fliers E, Faraone SV, et al. A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5; 147B(8):1536-46. doi: 10.1002/ajmg.b.30848 PMID: 18729135
29. Barkley RA, Smith KM, Fischer M, Navia B. An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood. Am J Med Genet B Neuropsychiatr Genet. 2006 Jul 5; 141B(5):487-98. PMID: 16741944
30. Elia J, Devoto M. ADHD genetics: 2007 update. Curr Psychiatry Rep. 2007 Oct; 9(5):434-9. PMID: 17915085
31. Franke B, Hoogman M, Arias Vasquez A, Heister JG, Savelkoul PJ, Naber M, et al. Association of the dopamine transporter (SLC6A3/DAT1) gene 9-6 haplotype with adult ADHD. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5; 147B(8):1576-9. doi: 10.1002/ajmg.b.30861 PMID: 18802924
32. Rohrer-Baumgartner N, Zeiner P, Eadie P, Egeland J, Gustavson K, Reichborn-Kjennerud T, et al. Language Delay in 3-Year-Old Children With ADHD Symptoms. J Atten Disord. 2013 Aug 13.
33. Magnus P, Irgens LM, Haug K, Nystad W, Skjaerven R, Stoltenberg C. Cohort profile: the Norwegian Mother and Child Cohort Study (MoBa). Int J Epidemiol. 2006 Oct; 35(5):1146-50. PMID: 16926217
34. Egger HL, Erkanli A, Keeler G, Potts E, Walter BK, Angold A. Test-Retest Reliability of the Preschool Age Psychiatric Assessment (PAPA). J Am Acad Child Adolesc Psychiatry. 2006 May; 45(5):538-49. PMID: 16601400
35. Athanasiu L, Mattingsdal M, Kahler AK, Brown A, Gustafsson O, Agartz I, et al. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J Psychiatr Res. 2010 Sep; 44(12):748-53. doi: 10.1016/j.jpsychires.2010.02.002 PMID: 20185149
36. Westlye LT, Walhovd KB, Dale AM, Bjornerud A, Due-Tonnessen P, Engvig A, et al. Life-span changes of the human brain white matter: diffusion tensor imaging (DTI) and volumetry. Cereb Cortex. 2010 Sep; 20(9):2055-68. doi: 10.1093/cercor/bhp280 PMID: 20032062
37. Tamnes CK, Ostby Y, Fjell AM, Westlye LT, Due-Tonnessen P, Walhovd KB. Brain maturation in adolescence and young adulthood: regional age-related changes in cortical thickness and white matter volume and microstructure. Cereb Cortex. 2010 Mar; 20(3):534-48. doi: 10.1093/cercor/bhp118 PMID: 19520764
38. Selnes P, Fjell AM, Gjerstad L, Bjornerud A, Wallin A, Due-Tonnessen P, et al. White matter imaging changes in subjective and mild cognitive impairment. Alzheimers Dement. 2012 Oct; 8(5 Suppl):S112-21. doi: 10.1016/j.jalz.2011.07.001 PMID: 23021621
39. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007 Sep; 81(3):559-75. PMID: 17701901
40. Devlin B, Roeder K. Genomic control for association studies. Biometrics. 1999 Dec; 55(4):997-1004. PMID: 11315092
41. Yang TP, Beazley C, Montgomery SB, Dimas AS, Gutierrez-Arcelus M, Stranger BE, et al. Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics. 2010 Oct 1; 26(19):2474-6. doi: 10.1093/bioinformatics/btq452 PMID: 20702402
42. Stranger BE, Montgomery SB, Dimas AS, Parts L, Stegle O, Ingle CE, et al. Patterns of cis regulatory variation in diverse human populations. PLoS Genet. 2012; 8(4):e1002639. doi: 10.1371/journal.pgen.1002639 PMID: 22532805
43. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011 Jan 7; 88(1):76-82. doi: 10.1016/j.ajhg.2010.11.011 PMID: 21167468
44. Lee PH, O'Dushlaine C, Thomas B, Purcell SM. INRICH: interval-based enrichment analysis for ge-nome- wide association studies. Bioinformatics. 2012 Jul 1; 28(13):1797-9. doi: 10.1093/bioinformatics/bts191 PMID: 22513993
45. Rossin EJ, Lage K, Raychaudhuri S, Xavier RJ, Tatar D, Benita Y, et al. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet. 2011; 7(1):e1001273. doi: 10.1371/journal.pgen.1001273 PMID: 21249183
46. Lips ES, Cornelisse LN, Toonen RF, Min JL, Hultman CM, Holmans PA, et al. Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia. Mol Psychiatry. 2012 Oct; 17 (10):996-1006. doi: 10.1038/mp.2011.117 PMID: 21931320
47. Hammerschlag AR, Polderman TJ, de Leeuw C, Tiemeier H, White T, Smit AB, et al. Functional gene-set analysis does not support a major role for synaptic function in attention deficit/hyperactivity disorder (ADHD). Genes (Basel). 2014; 5(3):604-14. doi: 10.3390/genes5030604 PMID: 25055203
48. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012 Nov 1; 491(7422):56-65. doi: 10.1038/nature11632 PMID: 23128226
49. Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, et al. The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry. 2006 Oct; 11(10):934-53. PMID: 16894395
50. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013 Apr 20; 381(9875):1371-9. doi: 10.1016/S0140-6736(12)62129-1 PMID: 23453885
51. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun; 21 (6):354-61. doi: 10.1016/j.tcb.2011.04.001 PMID: 21550244
52. Perkins DO, Jeffries C, Sullivan P. Expanding the 'central dogma': the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia. Mol Psychiatry. 2005 Jan; 10 (1):69-78. PMID: 15381925
53. Ning S, Zhao Z, Ye J, Wang P, Zhi H, Li R, et al. LincSNP: a database of linking disease-associated SNPs to human large intergenic non-coding RNAs. BMC Bioinformatics. 2014; 15(1):152.
54. Miyajima N, Maruyama S, Nonomura K, Hatakeyama S. TRIM36 interacts with the kinetochore protein CENP-H and delays cell cycle progression. Biochem Biophys Res Commun. 2009 Apr 10; 381(3):383-7. doi: 10.1016/j.bbrc.2009.02.059 PMID: 19232519
55. Yoshigai E, Kawamura S, Kuhara S, Tashiro K. Trim36/Haprin plays a critical role in the arrangement of somites during Xenopus embryogenesis. Biochem Biophys Res Commun. 2009 Jan 16; 378(3):428-32. doi: 10.1016/j.bbrc.2008.11.069 PMID: 19032936
56. Kitamura K, Tanaka H, Nishimune Y. Haprin, a novel haploid germ cell-specific RING finger protein involved in the acrosome reaction. J Biol Chem. 2003 Nov 7; 278(45):44417-23. PMID: 12917430
57. Xu B, Ionita-Laza I, Roos JL, Boone B, Woodrick S, Sun Y, et al. De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat Genet. 2012 Dec; 44(12):1365-9. doi: 10.1038/ng.2446 PMID: 23042115
58. Mavroconstanti T, Johansson S, Winge I, Knappskog PM, Haavik J. Functional properties of rare missense variants of human CDH13 found in adult attention deficit/hyperactivity disorder (ADHD) patients. PLoS One. 2013; 8(8):e71445. doi: 10.1371/journal.pone.0071445 PMID: 23936508
59. Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, et al. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 1993 Mar; 12(3):1161-7. PMID: 8384553
60. Buaas FW, Kirsh AL, Sharma M, McLean DJ, Morris JL, Griswold MD, et al. Plzf is required in adult male germ cells for stem cell self-renewal. Nat Genet. 2004 Jun; 36(6):647-52. PMID: 15156142
61. Costoya JA, Hobbs RM, Barna M, Cattoretti G, Manova K, Sukhwani M, et al. Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet. 2004 Jun; 36(6):653-9. PMID: 15156143
62. Fischer S, Kohlhase J, Bohm D, Schweiger B, Hoffmann D, Heitmann M, et al. Biallelic loss of function of the promyelocytic leukaemia zinc finger (PLZF) gene causes severe skeletal defects and genital hypoplasia. J Med Genet. 2008 Nov; 45(11):731-7. doi: 10.1136/jmg.2008.059451 PMID: 18611983
63. Weng J, Symons MN, Singh SM. Ethanol-responsive genes (Crtam, Zbtb16, and Mobp) located in the alcohol-QTL region of chromosome 9 are associated with alcohol preference in mice. Alcohol Clin Exp Res. 2009 Aug; 33(8):1409-16. doi: 10.1111/j.1530-0277.2009.00971.x PMID: 19413645
64. Haavik J, Halmoy A, Lundervold AJ, Fasmer OB. Clinical assessment and diagnosis of adults with attention-deficit/hyperactivity disorder. Expert Rev Neurother. 2010 Oct; 10(10):1569-80. doi: 10.1586/ern.10.149 PMID: 20925472
65. Elmer BM, McAllister AK. Major histocompatibility complex class I proteins in brain development and plasticity. Trends Neurosci. 2012 Nov; 35(11):660-70. doi: 10.1016/j.tins.2012.08.001 PMID: 22939644
66. van Gent T, Heijnen CJ, Treffers PD. Autism and the immune system. J Child Psychol Psychiatry. 1997 Mar; 38(3):337-49. PMID: 9232480
67. Gabbay V, Klein RG, Alonso CM, Babb JS, Nishawala M, De Jesus G, et al. Immune system dysregulation in adolescent major depressive disorder. J Affect Disord. 2009 May; 115(1-2):177-82.
68. Swedo SE, Leonard HL, Kiessling LS. Speculations on antineuronal antibody-mediated neuropsychiatric disorders of childhood. Pediatrics. 1994 Feb; 93(2):323-6. PMID: 8121747
69. Warren RP, Odell JD, Warren WL, Burger RA, Maciulis A, Daniels WW, et al. Reading disability, attention-deficit hyperactivity disorder, and the immune system. Science. 1995 May 12; 268(5212):786-8. PMID: 7754359
70. Fasmer OB, Halmoy A, Eagan TM, Oedegaard KJ, Haavik J. Adult attention deficit hyperactivity disorder is associated with asthma. BMC Psychiatry. 2011; 11:128. doi: 10.1186/1471-244X-11-128 PMID: 21819624
71. Ning S, Zhao Z, Ye J, Wang P, Zhi H, Li R, et al. LincSNP: a database of linking disease-associated SNPs to human large intergenic non-coding RNAs. BMC Bioinformatics. 2014; 15:152. doi: 10.1186/1471-2105-15-152 PMID: 24885522
72. Yang L, Neale BM, Liu L, Lee SH, Wray NR, Ji N, et al. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. Am J Med Genet B Neuropsychiatr Genet. 2013 Jul; 162B(5):419-30. doi: 10.1002/ajmg.b.32169 PMID: 23728934
73. Rao ML, Gross G, Strebel B, Halaris A, Huber G, Braunig P, et al. Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. Biol Psychiatry. 1994 Feb 1; 35(3):151-63. PMID: 7909693
74. Mansour HA, Talkowski ME, Wood J, Chowdari KV, McClain L, Prasad K, et al. Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia. Bipolar Disord. 2009 Nov; 11(7):701-10. doi: 10.1111/j.1399-5618.2009.00756.x PMID: 19839995
75. Baird AL, Coogan AN, Siddiqui A, Donev RM, Thome J. Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels. Mol Psychiatry. 2012 Oct; 17(10):988-95. doi: 10.1038/mp.2011.149 PMID: 22105622
76. Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013 Sep; 45(9):984-94. doi: 10.1038/ng.2711 PMID: 23933821
77. Fisher SE, Francks C, McCracken JT, McGough JJ, Marlow AJ, MacPhie IL, et al. A genomewide scan for loci involved in attention-deficit/hyperactivity disorder. Am J Hum Genet. 2002 May; 70(5):1183-96. PMID: 11923911
78. Lenartowski R, Goc A. Epigenetic, transcriptional and posttranscriptional regulation of the tyrosine hydroxylase gene. Int J Dev Neurosci. 2011 Dec; 29(8):873-83. doi: 10.1016/j.ijdevneu.2011.07.006 PMID: 21803145
79. Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M, et al. Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry. 2005 Oct; 10(10):944-9. PMID: 15940290
80. Walitza S, Renner TJ, Dempfle A, Konrad K, Wewetzer C, Halbach A, et al. Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder. Mol Psychiatry. 2005 Dec; 10(12):1126-32. PMID: 16116490
81. McKinney J, Johansson S, Halmoy A, Dramsdahl M, Winge I, Knappskog PM, et al. A loss-of-function mutation in tryptophan hydroxylase 2 segregating with attention-deficit/hyperactivity disorder. Mol Psychiatry. 2008 Apr; 13(4):365-7. doi: 10.1038/sj.mp.4002152 PMID: 18347598
82. Johansson S, Halmoy A, Mavroconstanti T, Jacobsen KK, Landaas ET, Reif A, et al. Common variants in the TPH1 and TPH2 regions are not associated with persistent ADHD in a combined sample of 1,636 adult cases and 1,923 controls from four European populations. Am J Med Genet B Neuropsychiatr Genet. 2010 Jul; 153B(5):1008-15. doi: 10.1002/ajmg.b.31067 PMID: 20213726
83. Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics. 2013 Sep; 45(9):984-+. doi: 10.1038/ng.2711 PMID: 23933821
84. McClellan J, King MC. Genetic heterogeneity in human disease. Cell. 2010 Apr 16; 141(2):210-7. doi: 10.1016/j.cell.2010.03.032 PMID: 20403315