Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD

Barbara Franke, Alejandro Arias Vasquez, Stefan Johansson, Martine Hoogman, Jasmin Romanos, Andrea Boreatti-Hümmer, Monika Heine, Christian P. Jacob, Klaus-Peter Lesch, Miguel Casas, Marta Ribasés, Rosa Bosch, Cristina Sánchez-Mora, Nria Gómez-Barros, Noèlia Fernndez-Castillo, M. nica Bayés, Anne Halmøy, Helene Halleland, Elisabeth T. Landaas, Ole B. Fasmer & 13 others Per M. Knappskog, Angelien J. G. A. M. Heister, Lambertus A. Kiemeney, J. J. Sandra Kooij, A. Marije Boonstra, Cees C. Kan, Philip Asherson, Stephen V. Faraone, Jan K. Buitelaar, Jan Haavik, Bru Cormand, Josep Antoni Ramos-Quiroga, Andreas Reif

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4-5% in children and 1-4% in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3′-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3′-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD. © 2010 Nature Publishing Group All rights reserved.
Original languageEnglish
Pages (from-to)656-664
JournalNeuropsychopharmacology
Volume35
Issue number3
DOIs
Publication statusPublished - 2010
Externally publishedYes

Cite this

Franke, Barbara ; Vasquez, Alejandro Arias ; Johansson, Stefan ; Hoogman, Martine ; Romanos, Jasmin ; Boreatti-Hümmer, Andrea ; Heine, Monika ; Jacob, Christian P. ; Lesch, Klaus-Peter ; Casas, Miguel ; Ribasés, Marta ; Bosch, Rosa ; Sánchez-Mora, Cristina ; Gómez-Barros, Nria ; Fernndez-Castillo, Noèlia ; Bayés, M. nica ; Halmøy, Anne ; Halleland, Helene ; Landaas, Elisabeth T. ; Fasmer, Ole B. ; Knappskog, Per M. ; Heister, Angelien J. G. A. M. ; Kiemeney, Lambertus A. ; Kooij, J. J. Sandra ; Boonstra, A. Marije ; Kan, Cees C. ; Asherson, Philip ; Faraone, Stephen V. ; Buitelaar, Jan K. ; Haavik, Jan ; Cormand, Bru ; Ramos-Quiroga, Josep Antoni ; Reif, Andreas. / Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD. In: Neuropsychopharmacology. 2010 ; Vol. 35, No. 3. pp. 656-664.
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title = "Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD",
abstract = "Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4-5{\%} in children and 1-4{\%} in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3′-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3′-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD. {\circledC} 2010 Nature Publishing Group All rights reserved.",
author = "Barbara Franke and Vasquez, {Alejandro Arias} and Stefan Johansson and Martine Hoogman and Jasmin Romanos and Andrea Boreatti-H{\"u}mmer and Monika Heine and Jacob, {Christian P.} and Klaus-Peter Lesch and Miguel Casas and Marta Ribas{\'e}s and Rosa Bosch and Cristina S{\'a}nchez-Mora and Nria G{\'o}mez-Barros and No{\`e}lia Fernndez-Castillo and Bay{\'e}s, {M. nica} and Anne Halm{\o}y and Helene Halleland and Landaas, {Elisabeth T.} and Fasmer, {Ole B.} and Knappskog, {Per M.} and Heister, {Angelien J. G. A. M.} and Kiemeney, {Lambertus A.} and Kooij, {J. J. Sandra} and Boonstra, {A. Marije} and Kan, {Cees C.} and Philip Asherson and Faraone, {Stephen V.} and Buitelaar, {Jan K.} and Jan Haavik and Bru Cormand and Ramos-Quiroga, {Josep Antoni} and Andreas Reif",
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Franke, B, Vasquez, AA, Johansson, S, Hoogman, M, Romanos, J, Boreatti-Hümmer, A, Heine, M, Jacob, CP, Lesch, K-P, Casas, M, Ribasés, M, Bosch, R, Sánchez-Mora, C, Gómez-Barros, N, Fernndez-Castillo, N, Bayés, MN, Halmøy, A, Halleland, H, Landaas, ET, Fasmer, OB, Knappskog, PM, Heister, AJGAM, Kiemeney, LA, Kooij, JJS, Boonstra, AM, Kan, CC, Asherson, P, Faraone, SV, Buitelaar, JK, Haavik, J, Cormand, B, Ramos-Quiroga, JA & Reif, A 2010, 'Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD' Neuropsychopharmacology, vol. 35, no. 3, pp. 656-664. https://doi.org/10.1038/npp.2009.170

Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD. / Franke, Barbara; Vasquez, Alejandro Arias; Johansson, Stefan; Hoogman, Martine; Romanos, Jasmin; Boreatti-Hümmer, Andrea; Heine, Monika; Jacob, Christian P.; Lesch, Klaus-Peter; Casas, Miguel; Ribasés, Marta; Bosch, Rosa; Sánchez-Mora, Cristina; Gómez-Barros, Nria; Fernndez-Castillo, Noèlia; Bayés, M. nica; Halmøy, Anne; Halleland, Helene; Landaas, Elisabeth T.; Fasmer, Ole B.; Knappskog, Per M.; Heister, Angelien J. G. A. M.; Kiemeney, Lambertus A.; Kooij, J. J. Sandra; Boonstra, A. Marije; Kan, Cees C.; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Haavik, Jan; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Reif, Andreas.

In: Neuropsychopharmacology, Vol. 35, No. 3, 2010, p. 656-664.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD

AU - Franke, Barbara

AU - Vasquez, Alejandro Arias

AU - Johansson, Stefan

AU - Hoogman, Martine

AU - Romanos, Jasmin

AU - Boreatti-Hümmer, Andrea

AU - Heine, Monika

AU - Jacob, Christian P.

AU - Lesch, Klaus-Peter

AU - Casas, Miguel

AU - Ribasés, Marta

AU - Bosch, Rosa

AU - Sánchez-Mora, Cristina

AU - Gómez-Barros, Nria

AU - Fernndez-Castillo, Noèlia

AU - Bayés, M. nica

AU - Halmøy, Anne

AU - Halleland, Helene

AU - Landaas, Elisabeth T.

AU - Fasmer, Ole B.

AU - Knappskog, Per M.

AU - Heister, Angelien J. G. A. M.

AU - Kiemeney, Lambertus A.

AU - Kooij, J. J. Sandra

AU - Boonstra, A. Marije

AU - Kan, Cees C.

AU - Asherson, Philip

AU - Faraone, Stephen V.

AU - Buitelaar, Jan K.

AU - Haavik, Jan

AU - Cormand, Bru

AU - Ramos-Quiroga, Josep Antoni

AU - Reif, Andreas

PY - 2010

Y1 - 2010

N2 - Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4-5% in children and 1-4% in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3′-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3′-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD. © 2010 Nature Publishing Group All rights reserved.

AB - Attention deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders with a worldwide prevalence around 4-5% in children and 1-4% in adults. Although ADHD is highly heritable and familial risk may contribute most strongly to the persistent form of the disorder, there are few studies on the genetics of ADHD in adults. In this paper, we present the first results of the International Multicentre Persistent ADHD Genetics CollaboraTion (IMpACT) that has been set up with the goal of performing research into the genetics of persistent ADHD. In this study, we carried out a combined analysis as well as a meta-analysis of the association of the SLC6A3/DAT1 gene with persistent ADHD in 1440 patients and 1769 controls from IMpACT and an earlier report. DAT1, encoding the dopamine transporter, is one of the most frequently studied genes in ADHD, though results have been inconsistent. A variable number tandem repeat polymorphism (VNTR) in the 3′-untranslated region (UTR) of the gene and, more recently, a haplotype of this VNTR with another VNTR in intron 8 have been the target of most studies. Although the 10/10 genotype of the 3′-UTR VNTR and the 10-6 haplotype of the two VNTRs are thought to be risk factors for ADHD in children, we found the 9/9 genotype and the 9-6 haplotype associated with persistent ADHD. In conclusion, a differential association of DAT1 with ADHD in children and in adults might help explain the inconsistencies observed in earlier association studies. However, the data might also imply that DAT1 has a modulatory rather than causative role in ADHD. © 2010 Nature Publishing Group All rights reserved.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/19890261

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