title: Genome-wide linkage analysis in a Dutch multigenerational family with attention deficit hyperactivity disorder.
abstract: Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder. Genetics has an important role in the aetiology of this disease. In this study, we describe the clinical findings in a Dutch family with eight patients suffering from ADHD, in whom five had at least one other psychiatric disorder. We performed a genome-wide (parametric and nonparametric) affected-only linkage analysis. Two genomic regions on chromosomes 7 and 14 showed an excess of allele sharing among the definitely affected members of the family with suggestive LOD scores (2.1 and 2.08). Nonparametric linkage analyses (NPL) yielded a maxNPL of 2.92 (P=0.001) for marker D7S502 and a maxNPL score of 2.56 (P=0.003) for marker D14S275. We confirmed that all patients share the same haplotype in each region of 7p15.1-q31.33 and 14q11.2-q22.3. Interestingly, both loci have been reported before in Dutch (affected sib pairs) and German (extended families) ADHD linkage studies. Hopefully, the genome-wide association studies in ADHD will help to highlight specific polymorphisms and genes within the broad areas detected by our, as well as other, linkage studies.
authors.affiliation: Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Rinus
authors.initials: R
authors.lastname: Vegt
authors.forename: Aida M
authors.initials: AM
authors.lastname: Bertoli-Avella
authors.forename: Joke H M
authors.initials: JH
authors.lastname: Tulen
authors.forename: Bianca
authors.initials: B
authors.lastname: de Graaf
authors.forename: Annemieke J M H
authors.initials: AJ
authors.lastname: Verkerk
authors.forename: Jeroen
authors.initials: J
authors.lastname: Vervoort
authors.forename: Carla M
authors.initials: CM
authors.lastname: Twigt
authors.forename: Anneke
authors.initials: A
authors.lastname: Maat-Kievit
authors.forename: Ruud
authors.initials: R
authors.lastname: van Tuijl
authors.forename: Marieke
authors.initials: M
authors.lastname: van der Lijn
authors.forename: Michiel W
authors.initials: MW
authors.lastname: Hengeveld
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002897:Chromosomes, Human, Pair 7; D015897:Comorbidity; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study / Q000379:methods*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009426:Netherlands; D010375:Pedigree
chemical_list: D005819:Genetic Markers
references.citation: Proc Natl Acad Sci U S A. 1989 Jun;86(11):4175-8
references.pmid: 2726769
references.citation: Mol Psychiatry. 2006 Feb;11(2):196-205
references.pmid: 16222334
references.citation: Genet Epidemiol. 2000 Jan;18(1):1-16
references.pmid: 10603455
references.citation: Mol Psychiatry. 2008 May;13(5):522-30
references.pmid: 18301393
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1345-54
references.pmid: 18821565
references.citation: Am J Hum Genet. 1997 Jun;60(6):1276-82
references.pmid: 9199546
references.citation: Am J Hum Genet. 1996 Jun;58(6):1323-37
references.pmid: 8651310
references.citation: Pediatrics. 1975 Mar;55(3):437-41
references.pmid: 1143984
references.citation: Am J Hum Genet. 2002 May;70(5):1183-96
references.pmid: 11923911
references.citation: Mol Psychiatry. 2006 Jan;11(1):5-8
references.pmid: 16205734
references.citation: Bioinformatics. 2005 May 15;21(10):2556-7
references.pmid: 15746282
references.citation: Nat Genet. 1995 Nov;11(3):241-7
references.pmid: 7581446
references.citation: J Am Acad Child Adolesc Psychiatry. 1997 Jun;36(6):737-44
references.pmid: 9183127
references.citation: Am J Hum Genet. 2003 May;72(5):1251-60
references.pmid: 12679898
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1392-8
references.pmid: 18988193
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1337-44
references.pmid: 18980221
references.citation: Arch Gen Psychiatry. 1992 Sep;49(9):728-38
references.pmid: 1514878
references.citation: Neuropsychopharmacology. 2002 Oct;27(4):607-19
references.pmid: 12377397
references.citation: Hum Hered. 2004;57(1):49-58
references.pmid: 15133312
references.citation: Arch Gen Psychiatry. 1973 Jun;28(6):888-91
references.pmid: 4707995
references.citation: Bioinformatics. 2005 Apr 15;21(8):1730-2
references.pmid: 15377505
references.citation: Science. 1999 Jan 15;283(5400):397-401
references.pmid: 9888856
references.citation: Behav Genet. 1994 May;24(3):193-205
references.pmid: 7945150
references.citation: Mol Psychiatry. 2003 Mar;8(3):299-308
references.pmid: 12660802
references.citation: Mol Psychiatry. 2008 May;13(5):514-21
references.pmid: 18180756
references.citation: Am J Hum Genet. 2008 Jul;83(1):99-105
references.pmid: 18599010
references.citation: Am J Psychiatry. 2001 Jul;158(7):1052-7
references.pmid: 11431226
references.citation: Hum Genet. 2009 Jul;126(1):51-90
references.pmid: 19506906
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):109-25
references.pmid: 15700344
references.citation: J Child Psychol Psychiatry. 1975 Jul;16(3):261-4
references.pmid: 1171894
references.citation: J Neural Transm (Vienna). 2008 Nov;115(11):1573-85
references.pmid: 18839057
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1387-91
references.pmid: 18081027
references.citation: J Clin Psychiatry. 2006;67 Suppl 8:13-20
references.pmid: 16961425
references.citation: Am J Hum Genet. 2004 Dec;75(6):998-1014
references.pmid: 15497111
references.citation: Eur J Hum Genet. 2009 Jul;17(7):958-66
references.pmid: 19156173
references.citation: Am J Addict. 2005 Jul-Sep;14(4):319-27
references.pmid: 16188712