Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations

Cristina Sánchez-Mora, Marta Ribasés, Miquel Casas, M. nica Bayés, Rosa Bosch, Noelia Fernàndez-Castillo, Lucas Brunso, Kaya K. Jacobsen, Elisabeth T. Landaas, Astri J. Lundervold, Silke Gross-Lesch, Susanne Kreiker, Christian P. Jacob, Klaus-Peter Lesch, Jan K. Buitelaar, Martine Hoogman, Lambertus A. L. M. Kiemeney, J. J. Sandra Kooij, Eric Mick, Phil Asherson & 7 others Stephen V. Faraone, Barbara Franke, Andreas Reif, Stefan Johansson, Jan Haavik, Josep Antoni Ramos-Quiroga, Bru Cormand

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4-8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120bp duplication in the promoter and 48bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple-marker meta-analysis showed a nominal association (P=0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3'UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene×gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. © 2011 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)600-612
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume156
Issue number5
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Sánchez-Mora, Cristina ; Ribasés, Marta ; Casas, Miquel ; Bayés, M. nica ; Bosch, Rosa ; Fernàndez-Castillo, Noelia ; Brunso, Lucas ; Jacobsen, Kaya K. ; Landaas, Elisabeth T. ; Lundervold, Astri J. ; Gross-Lesch, Silke ; Kreiker, Susanne ; Jacob, Christian P. ; Lesch, Klaus-Peter ; Buitelaar, Jan K. ; Hoogman, Martine ; Kiemeney, Lambertus A. L. M. ; Kooij, J. J. Sandra ; Mick, Eric ; Asherson, Phil ; Faraone, Stephen V. ; Franke, Barbara ; Reif, Andreas ; Johansson, Stefan ; Haavik, Jan ; Ramos-Quiroga, Josep Antoni ; Cormand, Bru. / Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2011 ; Vol. 156, No. 5. pp. 600-612.
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title = "Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations",
abstract = "Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4-8{\%} of children. ADHD persists into adulthood in around 65{\%} of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120bp duplication in the promoter and 48bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple-marker meta-analysis showed a nominal association (P=0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3'UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene×gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. {\circledC} 2011 Wiley-Liss, Inc.",
author = "Cristina S{\'a}nchez-Mora and Marta Ribas{\'e}s and Miquel Casas and Bay{\'e}s, {M. nica} and Rosa Bosch and Noelia Fern{\`a}ndez-Castillo and Lucas Brunso and Jacobsen, {Kaya K.} and Landaas, {Elisabeth T.} and Lundervold, {Astri J.} and Silke Gross-Lesch and Susanne Kreiker and Jacob, {Christian P.} and Klaus-Peter Lesch and Buitelaar, {Jan K.} and Martine Hoogman and Kiemeney, {Lambertus A. L. M.} and Kooij, {J. J. Sandra} and Eric Mick and Phil Asherson and Faraone, {Stephen V.} and Barbara Franke and Andreas Reif and Stefan Johansson and Jan Haavik and Ramos-Quiroga, {Josep Antoni} and Bru Cormand",
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pages = "600--612",
journal = "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics",
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Sánchez-Mora, C, Ribasés, M, Casas, M, Bayés, MN, Bosch, R, Fernàndez-Castillo, N, Brunso, L, Jacobsen, KK, Landaas, ET, Lundervold, AJ, Gross-Lesch, S, Kreiker, S, Jacob, CP, Lesch, K-P, Buitelaar, JK, Hoogman, M, Kiemeney, LALM, Kooij, JJS, Mick, E, Asherson, P, Faraone, SV, Franke, B, Reif, A, Johansson, S, Haavik, J, Ramos-Quiroga, JA & Cormand, B 2011, 'Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations' American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 156, no. 5, pp. 600-612. https://doi.org/10.1002/ajmg.b.31202

Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations. / Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miquel; Bayés, M. nica; Bosch, Rosa; Fernàndez-Castillo, Noelia; Brunso, Lucas; Jacobsen, Kaya K.; Landaas, Elisabeth T.; Lundervold, Astri J.; Gross-Lesch, Silke; Kreiker, Susanne; Jacob, Christian P.; Lesch, Klaus-Peter; Buitelaar, Jan K.; Hoogman, Martine; Kiemeney, Lambertus A. L. M.; Kooij, J. J. Sandra; Mick, Eric; Asherson, Phil; Faraone, Stephen V.; Franke, Barbara; Reif, Andreas; Johansson, Stefan; Haavik, Jan; Ramos-Quiroga, Josep Antoni; Cormand, Bru.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 156, No. 5, 2011, p. 600-612.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta-analysis in four European populations

AU - Sánchez-Mora, Cristina

AU - Ribasés, Marta

AU - Casas, Miquel

AU - Bayés, M. nica

AU - Bosch, Rosa

AU - Fernàndez-Castillo, Noelia

AU - Brunso, Lucas

AU - Jacobsen, Kaya K.

AU - Landaas, Elisabeth T.

AU - Lundervold, Astri J.

AU - Gross-Lesch, Silke

AU - Kreiker, Susanne

AU - Jacob, Christian P.

AU - Lesch, Klaus-Peter

AU - Buitelaar, Jan K.

AU - Hoogman, Martine

AU - Kiemeney, Lambertus A. L. M.

AU - Kooij, J. J. Sandra

AU - Mick, Eric

AU - Asherson, Phil

AU - Faraone, Stephen V.

AU - Franke, Barbara

AU - Reif, Andreas

AU - Johansson, Stefan

AU - Haavik, Jan

AU - Ramos-Quiroga, Josep Antoni

AU - Cormand, Bru

PY - 2011

Y1 - 2011

N2 - Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4-8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120bp duplication in the promoter and 48bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple-marker meta-analysis showed a nominal association (P=0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3'UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene×gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. © 2011 Wiley-Liss, Inc.

AB - Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4-8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120bp duplication in the promoter and 48bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple-marker meta-analysis showed a nominal association (P=0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3'UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene×gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. © 2011 Wiley-Liss, Inc.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/21595008

U2 - 10.1002/ajmg.b.31202

DO - 10.1002/ajmg.b.31202

M3 - Article

VL - 156

SP - 600

EP - 612

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

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

SN - 1552-4841

IS - 5

ER -