Please cite this article as follows: Chen W, Zhou K, Sham P, Franke B, Kuntsi J, Campbell D, Fleischman K, Knight J, Andreou P, Arnold R, Altink M, Boer F, Boholst MJ, Buschgens C, Butler L, Christiansen H, Fliers E, Howe-Forbes R, Gabriëls I, Heise A, Korn-Lubetzki I, Marco R, Medad S, Minderaa R, Müller UC, Mulligan A, Psychogiou L, Rommelse N, Sethna V, Uebel H, McGuffin P, Plomin R, Banaschewski T, Buitelaar J, Ebstein R, Eisenberg J, Gill M, Manor I, Miranda A, Mulas F, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Sonuga-Barke E, Steinhausen H-C, Taylor E, Thompson M, Faraone SV, Asherson P. 2008. DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores: A Sampling Strategy for QTL Linkage. Am J Med Genet Part B 147B:1450–1460.
DSM-IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage†
Article first published online: 11 JAN 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Special Issue: Special Issue on the Genetics of ADHD Dedicated to the Memory of Richard Todd
Volume 147B, Issue 8, pages 1450–1460, 5 December 2008
How to Cite
Chen, W., Zhou, K., Sham, P., Franke, B., Kuntsi, J., Campbell, D., Fleischman, K., Knight, J., Andreou, P., Arnold, R., Altink, M., Boer, F., Boholst, M. J., Buschgens, C., Butler, L., Christiansen, H., Fliers, E., Howe-Forbes, R., Gabriëls, I., Heise, A., Korn-Lubetzki, I., Marco, R., Medad, S., Minderaa, R., Müller, U. C., Mulligan, A., Psychogiou, L., Rommelse, N., Sethna, V., Uebel, H., McGuffin, P., Plomin, R., Banaschewski, T., Buitelaar, J., Ebstein, R., Eisenberg, J., Gill, M., Manor, I., Miranda, A., Mulas, F., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J., Sonuga-Barke, E., Steinhausen, H.-C., Taylor, E., Thompson, M., Faraone, S. V. and Asherson, P. (2008), DSM-IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage. Am. J. Med. Genet., 147B: 1450–1460. doi: 10.1002/ajmg.b.30672
- Issue published online: 18 NOV 2008
- Article first published online: 11 JAN 2008
- Manuscript Accepted: 22 OCT 2007
- Manuscript Received: 27 NOV 2006
- NIMH. Grant Number: R01MH062873
- attention deficit hyperactivity disorder (ADHD);
- quantitative trait locus (QTL);
- linkage study;
- quantitative genetics;
- DF analysis
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 (λsib) 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. © 2008 Wiley-Liss, Inc.