A common variant in DRD3 receptor is associated with autism spectrum disorder

Mariken de Krom; Wouter G Staal; Roel A Ophoff; Judith Hendriks; Jan Buitelaar; Barbara Franke; Maretha V de Jonge; Patrick Bolton; David Collier; Sarah Curran; Herman van Engeland; Jan M van Ree

doi:10.1016/j.biopsych.2008.09.035

A common variant in DRD3 receptor is associated with autism spectrum disorder

Mariken de Krom, Wouter G Staal, Roel A Ophoff, Judith Hendriks, Jan Buitelaar, Barbara Franke, Maretha V de Jonge, Patrick Bolton, David Collier, Sarah Curran, Herman van Engeland, Jan M van Ree

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

Abstract

BACKGROUND: The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study.

METHODS: 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample.

RESULTS: No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162).

CONCLUSIONS: The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.

Original language	English
Pages (from-to)	625-30
Number of pages	6
Journal	Biological Psychiatry
Volume	65
Issue number	7
DOIs	https://doi.org/10.1016/j.biopsych.2008.09.035
Publication status	Published - 1 Apr 2009

Keywords

Adolescent
Attention Deficit Disorder with Hyperactivity
Autistic Disorder
Child
Female
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Receptors, Dopamine D3

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title = "A common variant in DRD3 receptor is associated with autism spectrum disorder",

abstract = "BACKGROUND: The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study.METHODS: 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample.RESULTS: No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162).CONCLUSIONS: The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.",

keywords = "Adolescent, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Child, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Receptors, Dopamine D3",

author = "{de Krom}, Mariken and Staal, {Wouter G} and Ophoff, {Roel A} and Judith Hendriks and Jan Buitelaar and Barbara Franke and {de Jonge}, {Maretha V} and Patrick Bolton and David Collier and Sarah Curran and {van Engeland}, Herman and {van Ree}, {Jan M}",

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doi = "10.1016/j.biopsych.2008.09.035",

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T1 - A common variant in DRD3 receptor is associated with autism spectrum disorder

AU - de Krom, Mariken

AU - Staal, Wouter G

AU - Ophoff, Roel A

AU - Hendriks, Judith

AU - Buitelaar, Jan

AU - Franke, Barbara

AU - de Jonge, Maretha V

AU - Bolton, Patrick

AU - Collier, David

AU - Curran, Sarah

AU - van Engeland, Herman

AU - van Ree, Jan M

PY - 2009/4/1

Y1 - 2009/4/1

N2 - BACKGROUND: The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study.METHODS: 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample.RESULTS: No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162).CONCLUSIONS: The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.

AB - BACKGROUND: The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study.METHODS: 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample.RESULTS: No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162).CONCLUSIONS: The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.

KW - Adolescent

KW - Attention Deficit Disorder with Hyperactivity

KW - Autistic Disorder

KW - Child

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Receptors, Dopamine D3

U2 - 10.1016/j.biopsych.2008.09.035

DO - 10.1016/j.biopsych.2008.09.035

M3 - Article

C2 - 19058789

SN - 0006-3223

VL - 65

SP - 625

EP - 630

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 7

ER -

A common variant in DRD3 receptor is associated with autism spectrum disorder

Abstract

Keywords

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