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DSM-IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage

DSM-IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage
DSM-IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage
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 (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.
attention deficit hyperactivity disorder (ADHD), quantitative trait locus (QTL), linkage study, quantitative genetics, DF analysis
1552-4841
Chen, W.
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Zhou, K.
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Sham, P.
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Franke, B.
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Kuntsi, J.
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Campbell, D.
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Fleischman, K.
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Buschgens, C.
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Christiansen, H.
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Fliers, E.
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Gabriels, I.
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Heise, A.
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Minderaa, R.
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Müller, U.C.
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Miranda, A.
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Thompson, M.
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Faraone, S.V.
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Asherson, P.
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Chen, W.
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Zhou, K.
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Sham, P.
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Kuntsi, J.
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Fleischman, K.
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Knight, J.
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Andreou, P.
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Arnold, R.
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Altink, M.
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Boer, F.
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Boholst, M.J.
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Buschgens, C.
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Butler, L.
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Christiansen, H.
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Fliers, E.
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Howe-Forbes, R.
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Gabriels, I.
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Heise, A.
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Korn-Lubetzki, I.
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Marco, R.
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Medad, S.
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Minderaa, R.
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Mulligan, A.
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Psychogiou, L.
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Rommelse, N.
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Sethna, V.
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McGuffin, P.
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Plomin, R.
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Banaschewski, T.
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Buitelaar, J.
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Ebstein, R.
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Eisenberg, J.
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Gill, M.
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Miranda, A.
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Roeyers, H.
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Rothenberger, A.
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Sergeant, J.
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Sonuga-Barke, E.J.S.
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Steinhausen, H.C.
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Taylor, E.
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Thompson, M.
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Faraone, S.V.
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Asherson, P.
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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., Gabriels, 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.J.S., 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. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. (doi:10.1002/ajmg.b.30672).

Record type: Article

Abstract

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 (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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Published date: 2008
Keywords: attention deficit hyperactivity disorder (ADHD), quantitative trait locus (QTL), linkage study, quantitative genetics, DF analysis

Identifiers

Local EPrints ID: 54789
URI: https://eprints.soton.ac.uk/id/eprint/54789
ISSN: 1552-4841
PURE UUID: 929e4d42-8d55-41c6-8b5c-ef67e6a6c31f

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Date deposited: 04 Aug 2008
Last modified: 13 Mar 2019 20:38

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Contributors

Author: W. Chen
Author: K. Zhou
Author: P. Sham
Author: B. Franke
Author: J. Kuntsi
Author: D. Campbell
Author: K. Fleischman
Author: J. Knight
Author: P. Andreou
Author: R. Arnold
Author: M. Altink
Author: F. Boer
Author: M.J. Boholst
Author: C. Buschgens
Author: L. Butler
Author: H. Christiansen
Author: E. Fliers
Author: R. Howe-Forbes
Author: I. Gabriels
Author: A. Heise
Author: I. Korn-Lubetzki
Author: R. Marco
Author: S. Medad
Author: R. Minderaa
Author: U.C. Müller
Author: A. Mulligan
Author: L. Psychogiou
Author: N. Rommelse
Author: V. Sethna
Author: H. Uebel
Author: P. McGuffin
Author: R. Plomin
Author: T. Banaschewski
Author: J. Buitelaar
Author: R. Ebstein
Author: J. Eisenberg
Author: M. Gill
Author: I. Manor
Author: A. Miranda
Author: F. Mulas
Author: R.D. Oades
Author: H. Roeyers
Author: A. Rothenberger
Author: J. Sergeant
Author: E.J.S. Sonuga-Barke
Author: H.C. Steinhausen
Author: E. Taylor
Author: M. Thompson
Author: S.V. Faraone
Author: P. Asherson

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