title: Suggestive linkage of the child behavior checklist juvenile bipolar disorder phenotype to 1p21, 6p21, and 8q21.
abstract: OBJECTIVE
  Several studies have documented a profile of elevated scores on the Attention Problems, Aggressive Behavior and Anxious/Depressed scales of the Child Behavior Checklist (CBCL) in youth with bipolar disorder. The sum of these scales, referred to as the CBCL Juvenile Bipolar Disorder (JBD) phenotype, has modest diagnostic utility, and high scores are associated with severity of psychopathology and poor outcome. Recently, a genomewide linkage scan of this measure in ADHD sibling pairs revealed a region of suggestive linkage on chromosome 2q21. The current study aimed to further identify quantitative trait loci that influence the CBCL-JBD phenotype by using a dense and thus, arguably, more powerful set of single-nucleotide polymorphism markers in a different ADHD sibling pair sample.
  
  
  METHODS
  Subjects were 765 individuals from 154 families with CBCL data enrolled in a linkage study of ADHD. Linkage analyses were completed using a multipoint maximum likelihood variance components approach implemented using the statistical program SOLAR.
  
  
  RESULTS
  Heritability of the CBCL-JBD phenotype was estimated at .71. Although no regions of the genome surpassed empirically derived criteria for significant linkage (p = .000038), peaks on 1p21.1 (p = .00037; LOD = 2.76), 6p21.3 (p = .00054; LOD =2.60), and 8q21.13 (p = .00081; LOD = 2.44) surpassed the threshold for suggestive linkage (p = .002). These regions have been highlighted in genomewide scans of bipolar disorder in adults, schizophrenia, autism, and ADHD.
  
  
  CONCLUSIONS
  Findings raise the possibility that genes in these regions influence variation on the CBCL-JBD scale and the emotional and behavioral dysregulation associated with severe psychopathology.
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Harvard Medical School, Center for Human Genetics Research at Massachusetts General Hospital, Boston MA 02114, USA. aedoyle@partners.org
authors.forename: Alysa E
authors.initials: AE
authors.lastname: Doyle
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.forename: Manuel A R
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Patricia
authors.initials: P
authors.lastname: Wong
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
mesh_terms: D000293:Adolescent; D000374:Aggression; D001007:Anxiety; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics / Q000523:psychology; D057189:Checklist; D002648:Child; D002652:Child Behavior / Q000502:physiology / Q000523:psychology; D002653:Child Behavior Disorders / Q000235:genetics; D002878:Chromosomes, Human, Pair 1; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8; D003863:Depression; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D011569:Psychiatric Status Rating Scales; D040641:Quantitative Trait Loci; D012559:Schizophrenia / Q000235:genetics
chemical_list: D005819:Genetic Markers
references.citation: Biol Psychiatry. 2009 Jun 15;65(12):1055-62
references.pmid: 19251251
references.citation: Biol Psychiatry. 2006 Nov 1;60(9):903-11
references.pmid: 16650832
references.citation: Trends Neurosci. 2009 Feb;32(2):69-72
references.pmid: 19135727
references.citation: Am J Hum Genet. 1999 Aug;65(2):493-507
references.pmid: 10417292
references.citation: Am J Hum Genet. 2008 Feb;82(2):477-88
references.pmid: 18252227
references.citation: Arch Gen Psychiatry. 1982 Aug;39(8):879-83
references.pmid: 7103676
references.citation: Child Dev. 1985 Feb;56(1):265-75
references.pmid: 3987406
references.citation: J Affect Disord. 1998 Nov;51(2):93-100
references.pmid: 10743842
references.citation: Dialogues Clin Neurosci. 2008;10(2):215-28
references.pmid: 18689291
references.citation: Harv Rev Psychiatry. 1995 Nov-Dec;3(4):227-30
references.pmid: 9384951
references.citation: J Clin Psychiatry. 2009 Apr 21;70(5):732-40
references.pmid: 19389330
references.citation: Am J Psychiatry. 1994 Jul;151(7):1048-54
references.pmid: 8010363
references.citation: Am J Hum Genet. 2005 Dec;77(6):937-44
references.pmid: 16380906
references.citation: Biol Psychiatry. 2005 Oct 1;58(7):562-8
references.pmid: 16239161
references.citation: J Child Psychol Psychiatry. 2009 Mar;50(3):203-15
references.pmid: 19309325
references.citation: J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):107-125
references.pmid: 17195735
references.citation: Bipolar Disord. 2007 Dec;9(8):895-900
references.pmid: 18076540
references.citation: Am J Hum Genet. 2003 Jul;73(1):34-48
references.pmid: 12802786
references.citation: Mol Psychiatry. 2009 Mar;14(3):252-60
references.pmid: 19065143
references.citation: Am J Hum Genet. 1998 May;62(5):1198-211
references.pmid: 9545414
references.citation: J Affect Disord. 2009 Mar;113(3):227-35
references.pmid: 18632161
references.citation: Science. 2000 Apr 28;288(5466):678-82
references.pmid: 10784452
references.citation: Am J Hum Genet. 1995 May;56(5):1212-23
references.pmid: 7726179
references.citation: Mol Psychiatry. 2000 Nov;5(6):638-49
references.pmid: 11126394
references.citation: Mol Psychiatry. 2008 Jun;13(6):570-84
references.pmid: 18347602
references.citation: J Am Acad Child Adolesc Psychiatry. 2003 Dec;42(12):1494-503
references.pmid: 14627885
references.citation: Biol Psychiatry. 2003 Jun 1;53(11):1021-7
references.pmid: 12788247
references.citation: Child Psychiatry Hum Dev. 2007 Jun;38(1):47-55
references.pmid: 17160586
references.citation: Child Psychiatry Hum Dev. 1995 Fall;26(1):11-8
references.pmid: 7587476
references.citation: J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):867-76
references.pmid: 7649957
references.citation: Bipolar Disord. 2005 Dec;7(6):525-35
references.pmid: 16403178
references.citation: Mol Psychiatry. 2008 Jun;13(6):558-69
references.pmid: 18317468
references.citation: J Am Acad Child Adolesc Psychiatry. 2001 Sep;40(9):1094-102
references.pmid: 11556634
references.citation: Biol Psychiatry. 2007 Jul 15;62(2):115-20
references.pmid: 16950211
references.citation: Dev Psychopathol. 2004 Spring;16(2):461-76
references.pmid: 15487606
references.citation: Am J Psychiatry. 1995 Feb;152(2):271-3
references.pmid: 7840364
references.citation: J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):946-54; discussion 954-6
references.pmid: 7649966
references.citation: Biol Psychiatry. 2006 Nov 1;60(9):912-20
references.pmid: 16735031
references.citation: J Am Acad Child Adolesc Psychiatry. 2008 Oct;47(10):1151-7
references.pmid: 18724256
references.citation: J Child Psychol Psychiatry. 2009 Oct;50(10):1291-300
references.pmid: 19486226
references.citation: Am J Hum Genet. 2007 Nov;81(5):974-86
references.pmid: 17924339
references.citation: J Mol Neurosci. 2007;31(3):221-43
references.pmid: 17726228
references.citation: Biol Psychiatry. 2005 Oct 1;58(7):569-75
references.pmid: 15950197
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1399-411
references.pmid: 18973233
references.citation: Bipolar Disord. 2005 Dec;7(6):518-24
references.pmid: 16403177
references.citation: J Affect Disord. 1998 Nov;51(2):113-21
references.pmid: 10743844
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1387-91
references.pmid: 18081027
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11694-9
references.pmid: 17609372
references.citation: Curr Psychiatry Rep. 2002 Apr;4(2):146-52
references.pmid: 11914177
references.citation: Child Adolesc Psychiatr Clin N Am. 2009 Apr;18(2):441-53, x
references.pmid: 19264272
references.citation: Am J Psychiatry. 2008 Sep;165(9):1163-71
references.pmid: 18519524
references.citation: J Child Adolesc Psychopharmacol. 2003 Winter;13(4):471-88
references.pmid: 14977460
references.citation: J Paediatr Child Health. 1999 Apr;35(2):199-203
references.pmid: 10365361
references.citation: J Child Adolesc Psychopharmacol. 2009 Feb;19(1):23-30
references.pmid: 19232020
references.citation: J Psychiatr Res. 2002 Sep-Oct;36(5):337-45
references.pmid: 12127602
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1337-44
references.pmid: 18980221