Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD

K. Zhou; W. Chen; J.K. Buitelaar; T. Banaschewski; R.D. Oades; B. Franke; E. Sonuga-Barke; R. Ebstein; J. Eisenberg; M. Gill; I. Manor; A. Miranda; F. Mulas; H. Roeyers; A. Rothenberger; J.A. Sergeant; H.C. Steinhausen; J. Lasky-Su; E. Taylor; K. J. Brookes; X. Xu; B. Neale; F. Rijsdijk; M. Thompson; P. Asherson; S.V. Faraone

doi:10.1002/ajmg.b.30644

Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD

K. Zhou, W. Chen, J.K. Buitelaar, T. Banaschewski, R.D. Oades, B. Franke, E. Sonuga-Barke, R. Ebstein, J. Eisenberg, M. Gill, I. Manor, A. Miranda, F. Mulas, H. Roeyers, A. Rothenberger, J.A. Sergeant, H.C. Steinhausen, J. Lasky-Su, E. Taylor, K. J. BrookesX. Xu, B. Neale, F. Rijsdijk, M. Thompson, P. Asherson, S.V. Faraone

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Abstract

Previous studies have found heterogeneous association between DAT1-3′-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD. © 2007 Wiley-Liss, Inc.

Original language	English
Pages (from-to)	1481-1487
Number of pages	7
Journal	American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume	147B
Issue number	8
DOIs	https://doi.org/10.1002/ajmg.b.30644
Publication status	Published - 2008

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Zhou American Journal of Medical Genetics (Neuropsychiatric Genetics) 147B(8) 2008 uFinal published version, 147 KB

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Zhou, K., Chen, W., Buitelaar, J. K., Banaschewski, T., Oades, R. D., Franke, B., Sonuga-Barke, E., Ebstein, R., Eisenberg, J., Gill, M., Manor, I., Miranda, A., Mulas, F., Roeyers, H., Rothenberger, A., Sergeant, J. A., Steinhausen, H. C., Lasky-Su, J., Taylor, E., ... Faraone, S. V. (2008). Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B(8), 1481-1487. https://doi.org/10.1002/ajmg.b.30644

@article{9ffd560f3f054947855c7ec4259a3009,

title = "Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD",

abstract = "Previous studies have found heterogeneous association between DAT1-3′-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD. {\textcopyright} 2007 Wiley-Liss, Inc.",

author = "K. Zhou and W. Chen and J.K. Buitelaar and T. Banaschewski and R.D. Oades and B. Franke and E. Sonuga-Barke and R. Ebstein and J. Eisenberg and M. Gill and I. Manor and A. Miranda and F. Mulas and H. Roeyers and A. Rothenberger and J.A. Sergeant and H.C. Steinhausen and J. Lasky-Su and E. Taylor and Brookes, {K. J.} and X. Xu and B. Neale and F. Rijsdijk and M. Thompson and P. Asherson and S.V. Faraone",

year = "2008",

doi = "10.1002/ajmg.b.30644",

language = "English",

volume = "147B",

pages = "1481--1487",

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

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Zhou, K, Chen, W, Buitelaar, JK, Banaschewski, T, Oades, RD, Franke, B, Sonuga-Barke, E, Ebstein, R, Eisenberg, J, Gill, M, Manor, I, Miranda, A, Mulas, F, Roeyers, H, Rothenberger, A, Sergeant, JA, Steinhausen, HC, Lasky-Su, J, Taylor, E, Brookes, KJ, Xu, X, Neale, B, Rijsdijk, F, Thompson, M, Asherson, P & Faraone, SV 2008, 'Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD', American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, vol. 147B, no. 8, pp. 1481-1487. https://doi.org/10.1002/ajmg.b.30644

TY - JOUR

T1 - Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD

AU - Zhou, K.

AU - Chen, W.

AU - Buitelaar, J.K.

AU - Banaschewski, T.

AU - Oades, R.D.

AU - Franke, B.

AU - Sonuga-Barke, E.

AU - Ebstein, R.

AU - Eisenberg, J.

AU - Gill, M.

AU - Manor, I.

AU - Miranda, A.

AU - Mulas, F.

AU - Roeyers, H.

AU - Rothenberger, A.

AU - Sergeant, J.A.

AU - Steinhausen, H.C.

AU - Lasky-Su, J.

AU - Taylor, E.

AU - Brookes, K. J.

AU - Xu, X.

AU - Neale, B.

AU - Rijsdijk, F.

AU - Thompson, M.

AU - Asherson, P.

AU - Faraone, S.V.

PY - 2008

Y1 - 2008

N2 - Previous studies have found heterogeneous association between DAT1-3′-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD. © 2007 Wiley-Liss, Inc.

AB - Previous studies have found heterogeneous association between DAT1-3′-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD. © 2007 Wiley-Liss, Inc.

U2 - 10.1002/ajmg.b.30644

DO - 10.1002/ajmg.b.30644

M3 - Article

SN - 1552-4841

VL - 147B

SP - 1481

EP - 1487

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

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

IS - 8

ER -

Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD

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