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DSM-IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage. American Journal of Medical Genetics part B, 147B, 1450-1460. doi 10.1002/ajmg.b.30672 . (request a copy) (View Article)

Introduction: 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 & combined subtypes. --

Quantitative trait locus (QTL) approaches to linkage & 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.

Methods: To investigate the appropriateness of QTL approaches, we tested the familial association between 894 cases with a research diagnosis of DSM-IV ADHD combined type (ct) & continuous trait measures among 1,135 of their siblings unselected for phenotype.

1) The sibling recurrence rate for ADHDct was 12.7%, yielding a sibling recurrence risk ratio (lambda-sib) of 9.0.
2) Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples.
3) We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD cases.

That both affected & unaffected siblings contributed to the association with ADHD trait scores.

These data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined-type cases show familial association with dimensional ADHD symptom scores amongst their siblings.