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

Wai Chen; Kaixin Zhou; Pak Sham; Barbara Franke; Jonna Kuntsi; Desmond Campbell; Karin Fleischman; Jo Knight; Penny Andreou; Renée Arnold; Marieke Altink; Frits Boer; Mary Jane Boholst; Cathelijne Buschgens; Louise Butler; Hanna Christiansen; Ellen Fliers; Raoul Howe-Forbes; Isabel Gabriëls; Alexander Heise; Isabelle Korn-Lubetzki; Rafaela Marco; She'era Medad; Ruud Minderaa; Ueli C. Müller; Aisling Mulligan; Lamprini Psychogiou; Nanda Rommelse; Vaheshta Sethna; Henrik Uebel; Peter McGuffin; Robert Plomin; Tobias Banaschewski; Jan Buitelaar; Richard Ebstein; Jacques Eisenberg; Michael Gill; Iris Manor; Ana Miranda; Fernando Mulas; Robert D. Oades; Herbert Roeyers; Aribert Rothenberger; Joseph Sergeant; Edmund Sonuga-Barke; Hans Christoph Steinhausen; Eric Taylor; Margaret Thompson; Stephen V. Faraone; Philip Asherson

doi:10.1002/ajmg.b.30672

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

Wai Chen
, Kaixin Zhou
, Pak Sham
, Barbara Franke
, Jonna Kuntsi
, Desmond Campbell
, Karin Fleischman
, Jo Knight
, Penny Andreou
, Renée Arnold
, Marieke Altink
, Frits Boer
, Mary Jane Boholst
, Cathelijne Buschgens
, Louise Butler
, Hanna Christiansen
, Ellen Fliers
, Raoul Howe-Forbes
, Isabel Gabriëls
, Alexander Heise

Isabelle Korn-Lubetzki, Rafaela Marco, She'era Medad, Ruud Minderaa, Ueli C. Müller, Aisling Mulligan, Lamprini Psychogiou, Nanda Rommelse, Vaheshta Sethna, Henrik Uebel, Peter McGuffin, Robert Plomin, Tobias Banaschewski, Jan Buitelaar, Richard Ebstein, Jacques Eisenberg, Michael Gill, Iris Manor, Ana Miranda, Fernando Mulas, Robert D. Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Edmund Sonuga-Barke, Hans Christoph Steinhausen, Eric Taylor, Margaret Thompson, Stephen V. Faraone, Philip Asherson

Psychiatry

Upstate Medical University

King's College London
The University of Hong Kong
Radboud University Nijmegen
Center for Child and Adolescent Psychiatry
Department of Gastroenterology and Hepatology
Trinity College Dublin
University of Duisburg-Essen
BAVO-Europoort
Ghent University
University of Göttingen
Shaare Zedek Medical Center
University of Valencia
Geha Mental Health Center
University of Groningen
University of Zurich
University of Southampton
Vrije Universiteit Amsterdam
Zentralinstitut fur Seelische Gesundheit
Herzog Hospital Jerusalem
Hospital Universitario La Fe

Research output: Contribution to journal › Article › peer-review

134 Scopus citations

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 distributedthroughout 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 (λ_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.

Original language	English
Pages (from-to)	1450-1460
Number of pages	11
Journal	American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume	147
Issue number	8
DOIs	https://doi.org/10.1002/ajmg.b.30672
State	Published - Dec 5 2008

Keywords

Attention deficit hyperactivity disorder (ADHD)
DF analysis
Linkage study
Quantitative genetics
Quantitative trait locus (QTL)

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10.1002/ajmg.b.30672

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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., Gabriëls, I., ... 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, 147(8), 1450-1460. https://doi.org/10.1002/ajmg.b.30672

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

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 distributedthroughout 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.",

keywords = "Attention deficit hyperactivity disorder (ADHD), DF analysis, Linkage study, Quantitative genetics, Quantitative trait locus (QTL)",

author = "Wai Chen and Kaixin Zhou and Pak Sham and Barbara Franke and Jonna Kuntsi and Desmond Campbell and Karin Fleischman and Jo Knight and Penny Andreou and Ren{\'e}e Arnold and Marieke Altink and Frits Boer and Boholst, \{Mary Jane\} and Cathelijne Buschgens and Louise Butler and Hanna Christiansen and Ellen Fliers and Raoul Howe-Forbes and Isabel Gabri{\"e}ls and Alexander Heise and Isabelle Korn-Lubetzki and Rafaela Marco and She'era Medad and Ruud Minderaa and M{\"u}ller, \{Ueli C.\} and Aisling Mulligan and Lamprini Psychogiou and Nanda Rommelse and Vaheshta Sethna and Henrik Uebel and Peter McGuffin and Robert Plomin and Tobias Banaschewski and Jan Buitelaar and Richard Ebstein and Jacques Eisenberg and Michael Gill and Iris Manor and Ana Miranda and Fernando Mulas and Oades, \{Robert D.\} and Herbert Roeyers and Aribert Rothenberger and Joseph Sergeant and Edmund Sonuga-Barke and Steinhausen, \{Hans Christoph\} and Eric Taylor and Margaret Thompson and Faraone, \{Stephen V.\} and Philip Asherson",

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month = dec,

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doi = "10.1002/ajmg.b.30672",

language = "English",

volume = "147",

pages = "1450--1460",

journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",

issn = "1552-4841",

publisher = "Wiley-Liss Inc.",

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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, 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, HC, 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', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 147, no. 8, pp. 1450-1460. https://doi.org/10.1002/ajmg.b.30672

TY - JOUR

T1 - DSM-IV combined type ADHD shows familial association with sibling trait scores

T2 - A sampling strategy for QTL linkage

AU - Chen, Wai

AU - Zhou, Kaixin

AU - Sham, Pak

AU - Franke, Barbara

AU - Kuntsi, Jonna

AU - Campbell, Desmond

AU - Fleischman, Karin

AU - Knight, Jo

AU - Andreou, Penny

AU - Arnold, Renée

AU - Altink, Marieke

AU - Boer, Frits

AU - Boholst, Mary Jane

AU - Buschgens, Cathelijne

AU - Butler, Louise

AU - Christiansen, Hanna

AU - Fliers, Ellen

AU - Howe-Forbes, Raoul

AU - Gabriëls, Isabel

AU - Heise, Alexander

AU - Korn-Lubetzki, Isabelle

AU - Marco, Rafaela

AU - Medad, She'era

AU - Minderaa, Ruud

AU - Müller, Ueli C.

AU - Mulligan, Aisling

AU - Psychogiou, Lamprini

AU - Rommelse, Nanda

AU - Sethna, Vaheshta

AU - Uebel, Henrik

AU - McGuffin, Peter

AU - Plomin, Robert

AU - Banaschewski, Tobias

AU - Buitelaar, Jan

AU - Ebstein, Richard

AU - Eisenberg, Jacques

AU - Gill, Michael

AU - Manor, Iris

AU - Miranda, Ana

AU - Mulas, Fernando

AU - Oades, Robert D.

AU - Roeyers, Herbert

AU - Rothenberger, Aribert

AU - Sergeant, Joseph

AU - Sonuga-Barke, Edmund

AU - Steinhausen, Hans Christoph

AU - Taylor, Eric

AU - Thompson, Margaret

AU - Faraone, Stephen V.

AU - Asherson, Philip

PY - 2008/12/5

Y1 - 2008/12/5

N2 - 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 distributedthroughout 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.

AB - 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 distributedthroughout 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.

KW - Attention deficit hyperactivity disorder (ADHD)

KW - DF analysis

KW - Linkage study

KW - Quantitative genetics

KW - Quantitative trait locus (QTL)

UR - https://www.scopus.com/pages/publications/57349174136

U2 - 10.1002/ajmg.b.30672

DO - 10.1002/ajmg.b.30672

M3 - Article

C2 - 18189238

SN - 1552-4841

VL - 147

SP - 1450

EP - 1460

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 8

ER -

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

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Keywords

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