Copy number variants in attention-deficit hyperactive disorder: Identification of the 15q13 deletion and its functional role

Psychiatric Genetics

Volumn 25, Issue 2, 2015, Pages 59-70

  Valbonesi, Stefano ^a   Magri, Chiara ^c   Traversa, Michele ^c   Faraone, Stephen V ^e   Cattaneo, Annamaria ^b,f   Milanesi, Elena ^a,g   Valenti, Vera ^d   Gennarelli, Massimo ^a,c   Scassellati, Catia ^a  

^a IRCCS ISTITUTO CENTRO SAN GIOVANNI DI DIO FATEBENEFRATELLI   (Italy)

^b Neuropsychopharmacology Unit   (Italy)

^c UNIVERSITY OF BRESCIA   (Italy)

^d Childhood and Adolescent Neuropsychiatry Unit of Fatebenefratelli and Oftalmico   (Italy)

^e SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

^f KING'S COLLEGE LONDON   (United Kingdom)

^g TEL AVIV UNIVERSITY   (Israel)

Author keywords

attention deficit hyperactivity disorder; blood transcriptomics; copy number variant

Indexed keywords

ARTICLE; ATTENTION DEFICIT DISORDER; CHILD; CHROMOSOME 15Q; CHROMOSOME DELETION; CLINICAL ARTICLE; CONTROLLED STUDY; COPY NUMBER VARIATION; DOWN REGULATION; FEMALE; GENE EXPRESSION; GENETIC ANALYSIS; HUMAN; ITALIAN (CITIZEN); MALE; OXIDATIVE STRESS; PRIORITY JOURNAL; SCHOOL CHILD; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCRIPTOMICS; ADOLESCENT; CASE CONTROL STUDY; CHROMOSOME 15; DNA MICROARRAY; GENE EXPRESSION PROFILING; GENETICS;

ADOLESCENT; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; CASE-CONTROL STUDIES; CHILD; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 15; DNA COPY NUMBER VARIATIONS; FEMALE; GENE EXPRESSION PROFILING; HUMANS; MALE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS;

EID: 84924809876     PISSN: 09558829     EISSN: 14735873     Source Type: Journal    
DOI: 10.1097/YPG.0000000000000056     Document Type: Article

References (56)

1. Al-Yagon M, Cavendish W, Cornoldi C, Fawcett AJ, Grünke M, Hung LY, et al. (2013). The proposed changes for DSM-5 for SLD and ADHD: international perspectives-Australia, Germany, Greece, India, Israel, Italy, Spain, Taiwan, United Kingdom, and United States. J Learn Disabil 46:58-72.
2. American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, text revision. 4th ed. Washington DC: American Psychiatric Association.
3. Barlic J, Murphy PM (2007). Chemokine regulation of atherosclerosis. J Leukoc Biol 82:226-236.
4. Benfante R, Antonini RA, De Pizzol M, Gotti C, Clementi F, Locati M, Fornasari D (2011). Expression of the α7 nAChR subunit duplicate form (CHRFAM7A) is down-regulated in the monocytic cell line THP-1 on treatment with LPS. J Neuroimmunol 230:74-84.
5. Ben-Shachar S, Lanpher B, German JR, Qasaymeh M, Potocki L, Nagamani SC, et al. (2009). Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J Med Genet 46:382-388.
6. Biancardi A, Stoppa E (1997). Modified Campanelle Test (MCT), a test for the study of Attention in developmental age. Child Adolesc Psychiatry 64:73-84.
7. Bianchini R, Postorino V, Grasso R, Santoro B, Migliore S, Burl C, et al. (2013). Prevalence of ADHD in a sample of Italian students: a populationbased study. Res Dev Disabil 34:2543-2550.
8. Ceylan MF, Sener S, Bayraktar AC, Kavutcu M (2012). Changes in oxidative stress and cellular immunity serum markers in attention-deficit/hyperactivity disorder. Psychiatry Clin Neurosci 66:220-226. Cross-Disorder Group of the Psychiatric Genomics Consortium
9. Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, et al. (2013). Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet, 381, 1371-1379.
10. Dibbens LM, Mullen S, Helbig I, Mefford HC, Bayly MA, Bellows S, et al. EPICURE Consortium (2009). Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum Mol Genet 18:3626-3631.
11. Donev R, Thome J (2010). Inflammation: good or bad for ADHD? Atten Defic Hyperact Disord 2:257-266.
12. Elia J, Gai X, Xie HM, Perin JC, Geiger E, Glessner JT, et al. (2010). Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry 15:637-646.
13. Faraone SV, Mick E (2010). Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin North Am 33:159-180.
14. Fasmer OB, Riise T, Eagan TM, Lund A, Dilsaver SC, Hundal O, Oedegaard KJ (2011). Comorbidity of asthma with ADHD. J Atten Disord 15:564-571.
15. Ghanizadeh A, Berk M, Farrashbandi H, Alavi Shoushtari A, Villagonzalo KA (2013). Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach. Mitochondrion 13:515-519.
16. Gibney SM, Drexhage HA (2013). Evidence for a dysregulated immune system in the etiology of psychiatric disorders. J Neuroimmune Pharmacol 8:900-920.
17. Gizer IR, Ficks C,Waldman ID (2009). Candidate gene studies of ADHD: a metaanalytic review. Hum Genet 126:51-90.
18. Gladkevich A, Kauffman HF, Korf J (2004). Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 28:559-576.
19. Guan ZZ, Zhang X, Mousavi M, Tian JY, Unger C, Nordberg A (2001). Reduced expression of neuronal nicotinic acetylcholine receptors during the early stages of damage by oxidative stress in PC12 cells. J Neurosci Res 66:551-558.
20. Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, et al. (2009). 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 41:160-162.
21. Hoppman-Chaney N, Wain K, Seger PR, Superneau DW, Hodge JC (2013). Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. Clin Genet 83:345-351.
22. Joseph N, Zhang-James Y, Perl A, Faraone SV (2013). Oxidative stress and ADHD: a meta-analysis. J Attention Disord (in press).
23. Kwon HJ, Lee MY, Ha M, Yoo SJ, Paik KC, Lim JH, et al. (2014). The associations between ADHD and asthma in Korean children. BMC Psychiatry 14:70.
24. Le Pichon JB, Yu S, Kibiryeva N, Graf WD, Bittel DC (2013). Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome. Eur J Hum Genet 21:1093-1099.
25. Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, et al. Cross- Disorder Group of the Psychiatric Genomics Consortium; International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) (2013). Genetic relationship between five psychiatric disorders estimated from genomewide SNPs. Nat Genet 45:984-994.
26. Lin YL, Liu CC, Chuang JI, Lei HY, Yeh TM, Lin YS, et al. (2000). Involvement of oxidative stress, NF-IL-6, and RANTES expression in dengue-2-virus-infected human liver cells. Virology 276:114-126.
27. Lionel AC, Crosbie J, Barbosa N, Goodale T, Thiruvahindrapuram B, Rickaby J, et al. (2011). Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. Sci Transl Med 3:95ra75.
28. Marc DT, Ailts JW, Campeau DC, Bull MJ, Olson KL (2011). Neurotransmitters excreted in the urine as biomarkers of nervous system activity: validity and clinical applicability. Neurosci Biobehav Rev 35:635-644.
29. Miller DT, Shen Y, Weiss LA, Korn J, Anselm I, Bridgemohan C, et al. (2009). Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet 46:242-248.
30. Mogensen N, Larsson H, Lundholm C, Almqvist C (2011). Association between childhood asthma and ADHD symptoms in adolescence - a prospective population-based twin study. Allergy 66:1224-1230.
31. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. (2003). PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267-273.
32. Moskvina V, Craddock N, Holmans P, Nikolov I, Pahwa JS, Green E, et al. Wellcome Trust Case Control Consortium (2009). Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol Psychiatry 14:252-260.
33. Neale BM, Medland SE, Ripke S, Asherson P, Franke B, Lesch KP, et al. Psychiatric GWAS Consortium: ADHD Subgroup (2010). Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49:884-897.
34. Outram SV, Gordon AR, Hager-Theodorides AL, Metcalfe J, Crompton T, Kemp P (2008). KLF13 influences multiple stages of both B and T cell development. Cell Cycle 7:2047-2055.
35. Pagnamenta AT, Wing K, Sadighi Akha E, Knight SJ, Blte S, Schmtzer G, et al. International Molecular Genetic Study of Autism Consortium (2009). A 15q13.3 microdeletion segregating with autism. Eur J Hum Genet 17:687-692.
36. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942-948.
37. Rollins B, Martin MV, Morgan L, Vawter MP (2010). Analysis of whole genome biomarker expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 153B:919-936.
38. Sato KZ, Fujii T,Watanabe Y, Yamada S, Ando T, Kazuko F, Kawashima K (1999). Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. Neurosci Lett 266:17-20.
39. Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (2012). Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and metaanalyses. J Am Acad Child Adolesc Psychiatry 51:1003-1019.
40. Sharp AJ, Mefford HC, Li K, Baker C, Skinner C, Stevenson RE, et al. (2008). A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet 40:322-328.
41. Shinawi M, Schaaf CP, Bhatt SS, Xia Z, Patel A, Cheung SW, et al. (2009). A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nat Genet 41:1269-1271.
42. Song A, Chen YF, Thamatrakoln K, Storm TA, Krensky AM (1999). RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. Immunity 10:93-103.
43. Stefansson H, Rujescu D, Cichon S, Pietilinen OP, Ingason A, Steinberg S, et al. GROUP (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455:232-236.
44. Stephens SH, Franks A, Berger R, Palionyte M, Fingerlin TE, Wagner B, et al. (2012). Multiple genes in the 15q13-q14 chromosomal region are associated with schizophrenia. Psychiatr Genet 22:1-14.
45. Stergiakouli E, Hamshere M, Holmans P, Langley K, Zaharieva I, Hawi Z, et al. deCODE Genetics; Psychiatric GWAS Consortium (2012). Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. Am J Psychiatry 169:186-194.
46. Stone JL, ODonovan MC, Gurling H. International Schizophrenia Consortium (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237-241.
47. Sullivan PF, Fan C, Perou CM (2006). Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 141B:261-268.
48. Tripathy D, Thirumangalakudi L, Grammas P (2007). Expression of macrophage inflammatory protein 1-alpha is elevated in Alzheimers vessels and is regulated by oxidative stress. J Alzheimers Dis 11:447-455.
49. Tripathy D, Thirumangalakudi L, Grammas P (2010). RANTES upregulation in the Alzheimers disease brain: a possible neuroprotective role. Neurobiol Aging 31:8-16.
50. Van Bon BW, Mefford HC, Menten B, Koolen DA, Sharp AJ, Nillesen WM, et al. (2009). Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet 46:511-523.
51. Van der Zanden EP, Hilbers FW, Verseijden C, van den Wijngaard RM, Skynner M, Lee K, et al. (2012). Nicotinic acetylcholine receptor expression and susceptibility to cholinergic immunomodulation in human monocytes of smoking individuals. Neuroimmunomodulation 19:255-265.
52. Vukelic M, Qing X, Redecha P, Koo G, Salmon JE (2013). Cholinergic receptors modulate immune complex-induced inflammation in vitro and in vivo. J Immunol 191:1800-1807.
53. Williams NM, Zaharieva I, Martin A, Langley K, Mantripragada K, Fossdal R, et al. (2010). Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 376:1401-1408.
54. Williams NM, Franke B, Mick E, Anney RJ, Freitag CM, Gill M, et al. (2012). 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 169:195-204.
55. Wu JQ, Kosten TR, Zhang XY (2013). Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 46:200-206.
56. Yang L, Neale BM, Liu L, Lee SH, Wray NR, Ji N, et al. Psychiatric GWAS Consortium: ADHD Subgroup (2013). 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 162B:419-430.