DSM-IV combined type ADHD shows familial association with sibling trait scores: a sampling strategy for QTL linkage.
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Publication year
2008Author(s)
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American Journal of Medical Genetics. Part B : Neuropsychiatric Genetics, 147B, 8, (2008), pp. 1450-60ISSN
Publication type
Article / Letter to editor
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Organization
Psychiatry
Human Genetics
Journal title
American Journal of Medical Genetics. Part B : Neuropsychiatric Genetics
Volume
vol. 147B
Issue
iss. 8
Page start
p. 1450
Page end
p. 60
Subject
DCN 1: Perception and Action; DCN 2: Functional Neurogenomics; DCN 3: Neuroinformatics; IGMD 3: Genomic disorders and inherited multi-system disorders; NCEBP 9: Mental health; NCMLS 6: Genetics and epigenetic pathways of disease; UMCN 3.2: Cognitive neurosciences; UMCN 5.1: Genetic defects of metabolismAbstract
Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM-IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (lambda(sib)) of 9.0. Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADHD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings.
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- Faculty of Medical Sciences [90359]
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