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The dopamine receptor D4 7-repeat allele and prenatal smoking in ADHD-affected children and their unaffected siblings: no gene–environment interaction

The dopamine receptor D4 7-repeat allele and prenatal smoking in ADHD-affected children and their unaffected siblings: no gene–environment interaction
The dopamine receptor D4 7-repeat allele and prenatal smoking in ADHD-affected children and their unaffected siblings: no gene–environment interaction
Background: The dopamine receptor D4 (DRD4) 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (G×E) interaction of the DRD4 7-repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7-repeat allele differs between ADHD affected and unaffected children.
Methods: Linear mixed models were used to assess main and interactive effects of the DRD4 7-repeat allele and smoking during pregnancy in 539 ADHD-affected children and their 407 unaffected siblings, aged 6–17 years.
Results: There was some evidence pointing to differential effects of the DRD4 7-repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for G×E interactions.
Conclusion: Despite the large sample size, no G×E interactions were found. The impact of the DRD4 7-repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in rater-specific behaviors.
dopamine receptor d4 gene, attention deficit hyperactivity disorder (adhd), maternal smoking during pregnancy, gene by environment interaction
0021-9630
1053-1060
Altink, Marieke E.
55df7252-b071-4199-94db-a4c4729a8024
Arias-Vásquez, Alejandro
5ed767eb-ca5e-49d8-8535-3a2f95fcf396
Franke, Barbara
f71c8989-a108-40c4-a159-80a1e60b56bf
Slaats-Willemse, Dorine I.E.
f0e0ba7a-f6ea-4a7b-8a01-0eb7cfd64782
Buschgens, Cathelijne J.M.
8fe32fca-b674-40d2-9a2e-a415df5132d1
Rommelse, Nanda N.J.
19034ee6-8d12-4453-a6d0-317b40969bcf
Fliers, Ellen A.
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Anney, Richard
f0662844-38ae-47e1-8077-8aef1855a617
Brookes, Keeley-Joanne
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Chen, Wai
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Gill, Michael
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Mulligan, Aisling
79696570-6acc-4f76-bdfa-2854c134c531
Sonuga-Barke, Edmund
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Thompson, Margaret
bfe8522c-b252-4771-8036-744e93357c67
Sergeant, Joseph A.
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Faraone, Stephen V.
bd307516-e8db-4d38-b649-9d7d7caafe93
Asherson, Philip
a734c1f6-f31a-450b-81c3-ba7bb373e147
Buitelaar, Jan K.
a2e08a14-4de4-419e-9ea8-1e97ebbdddba
Altink, Marieke E.
55df7252-b071-4199-94db-a4c4729a8024
Arias-Vásquez, Alejandro
5ed767eb-ca5e-49d8-8535-3a2f95fcf396
Franke, Barbara
f71c8989-a108-40c4-a159-80a1e60b56bf
Slaats-Willemse, Dorine I.E.
f0e0ba7a-f6ea-4a7b-8a01-0eb7cfd64782
Buschgens, Cathelijne J.M.
8fe32fca-b674-40d2-9a2e-a415df5132d1
Rommelse, Nanda N.J.
19034ee6-8d12-4453-a6d0-317b40969bcf
Fliers, Ellen A.
1d06448c-7179-419c-bf82-4fb84035ffe3
Anney, Richard
f0662844-38ae-47e1-8077-8aef1855a617
Brookes, Keeley-Joanne
7a6bf948-c291-415f-8ed5-51b28a81deec
Chen, Wai
ad64ca20-e814-4c31-a0ce-230287a988d4
Gill, Michael
408d1dfa-5205-4e50-8130-7b26aa8288e8
Mulligan, Aisling
79696570-6acc-4f76-bdfa-2854c134c531
Sonuga-Barke, Edmund
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Thompson, Margaret
bfe8522c-b252-4771-8036-744e93357c67
Sergeant, Joseph A.
fca17df1-498d-4009-b445-dc6033711ab0
Faraone, Stephen V.
bd307516-e8db-4d38-b649-9d7d7caafe93
Asherson, Philip
a734c1f6-f31a-450b-81c3-ba7bb373e147
Buitelaar, Jan K.
a2e08a14-4de4-419e-9ea8-1e97ebbdddba

Altink, Marieke E., Arias-Vásquez, Alejandro, Franke, Barbara, Slaats-Willemse, Dorine I.E., Buschgens, Cathelijne J.M., Rommelse, Nanda N.J., Fliers, Ellen A., Anney, Richard, Brookes, Keeley-Joanne, Chen, Wai, Gill, Michael, Mulligan, Aisling, Sonuga-Barke, Edmund, Thompson, Margaret, Sergeant, Joseph A., Faraone, Stephen V., Asherson, Philip and Buitelaar, Jan K. (2008) The dopamine receptor D4 7-repeat allele and prenatal smoking in ADHD-affected children and their unaffected siblings: no gene–environment interaction. Journal of Child Psychology & Psychiatry, 49 (10), 1053-1060. (doi:10.1111/j.1469-7610.2008.01998.x).

Record type: Article

Abstract

Background: The dopamine receptor D4 (DRD4) 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (G×E) interaction of the DRD4 7-repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7-repeat allele differs between ADHD affected and unaffected children.
Methods: Linear mixed models were used to assess main and interactive effects of the DRD4 7-repeat allele and smoking during pregnancy in 539 ADHD-affected children and their 407 unaffected siblings, aged 6–17 years.
Results: There was some evidence pointing to differential effects of the DRD4 7-repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for G×E interactions.
Conclusion: Despite the large sample size, no G×E interactions were found. The impact of the DRD4 7-repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in rater-specific behaviors.

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Published date: October 2008
Keywords: dopamine receptor d4 gene, attention deficit hyperactivity disorder (adhd), maternal smoking during pregnancy, gene by environment interaction

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Local EPrints ID: 63813
URI: https://eprints.soton.ac.uk/id/eprint/63813
ISSN: 0021-9630
PURE UUID: abc19e65-559f-490f-b04b-9292292d8b54

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Date deposited: 05 Nov 2008
Last modified: 10 May 2019 16:30

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Contributors

Author: Marieke E. Altink
Author: Alejandro Arias-Vásquez
Author: Barbara Franke
Author: Dorine I.E. Slaats-Willemse
Author: Cathelijne J.M. Buschgens
Author: Nanda N.J. Rommelse
Author: Ellen A. Fliers
Author: Richard Anney
Author: Keeley-Joanne Brookes
Author: Wai Chen
Author: Michael Gill
Author: Aisling Mulligan
Author: Edmund Sonuga-Barke
Author: Margaret Thompson
Author: Joseph A. Sergeant
Author: Stephen V. Faraone
Author: Philip Asherson
Author: Jan K. Buitelaar

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