A Common Variant in DRD3 Receptor Is Associated with Autism Spectrum Disorder

M. de Krom; W.G. Staal; R.A. Ophoff; J. Hendriks; J.K. Buitelaar; B. Franke; M.V. de Jonge; P.F. Bolton; D.A. Collier; S. Curran; H. van Engeland; J.M. van Ree

doi:10.1016/j.biopsych.2008.09.035

A Common Variant in DRD3 Receptor Is Associated with Autism Spectrum Disorder

M. de Krom, W.G. Staal, R.A. Ophoff, J. Hendriks, J.K. Buitelaar, B. Franke, M.V. de Jonge, P.F. Bolton, D.A. Collier, S. Curran, H. van Engeland, J.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 in = 144) and ADHD in = 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 in 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)	625-630
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 - 2009

Keywords

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
GENOME-WIDE ASSOCIATION
GENETICS
LINKAGE

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10.1016/j.biopsych.2008.09.035

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@article{a0371144368e425199ca983a38c7562e,

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 in = 144) and ADHD in = 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 in 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 = "ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, GENOME-WIDE ASSOCIATION, GENETICS, LINKAGE",

author = "\{de Krom\}, M. and W.G. Staal and R.A. Ophoff and J. Hendriks and J.K. Buitelaar and B. Franke and \{de Jonge\}, M.V. and P.F. Bolton and D.A. Collier and S. Curran and \{van Engeland\}, H. and \{van Ree\}, J.M.",

year = "2009",

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

language = "English",

volume = "65",

pages = "625--630",

journal = "Biological Psychiatry",

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T1 - A Common Variant in DRD3 Receptor Is Associated with Autism Spectrum Disorder

AU - de Krom, M.

AU - Staal, W.G.

AU - Ophoff, R.A.

AU - Hendriks, J.

AU - Buitelaar, J.K.

AU - Franke, B.

AU - de Jonge, M.V.

AU - Bolton, P.F.

AU - Collier, D.A.

AU - Curran, S.

AU - van Engeland, H.

AU - van Ree, J.M.

PY - 2009

Y1 - 2009

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 in = 144) and ADHD in = 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 in 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 in = 144) and ADHD in = 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 in 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 - ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

KW - GENOME-WIDE ASSOCIATION

KW - GENETICS

KW - LINKAGE

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

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Keywords

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