Linkage and candidate gene studies of autism spectrum disorders in European populations

R. Holt; G. Barnby; E. Maestrini; E. Bacchelli; D. Brocklebank; I. Sousa; E. Mulder; K. Kantojarvi; I. Jarvela; S.M. Klauck; F Poustka; A.J. Bailey; H. van Engeland; M.V. de Jonge; X et al.; A.P. Monaco

doi:10.1038/ejhg.2010.69

Linkage and candidate gene studies of autism spectrum disorders in European populations

R. Holt, G. Barnby, E. Maestrini, E. Bacchelli, D. Brocklebank, I. Sousa, E. Mulder, K. Kantojarvi, I. Jarvela, S.M. Klauck, F Poustka, A.J. Bailey, H. van Engeland, M.V. de Jonge, X et al., A.P. Monaco

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

Abstract

Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 x 10(-5)) and between SND1 and strict autism (rs1881084, P=7.76 x 10(-5)) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1. European Journal of Human Genetics (2010) 18, 1013-1019; doi:10.1038/ejhg.2010.69; published online 5 May 2010

Original language	English
Pages (from-to)	1013-1019
Number of pages	7
Journal	European Journal of Human Genetics
Volume	18
Issue number	9
DOIs	https://doi.org/10.1038/ejhg.2010.69
Publication status	Published - 10 Sept 2010

Keywords

autistic disorder
linkage
association
candidate gene
PERVASIVE DEVELOPMENTAL DISORDERS
FAMILY-BASED ASSOCIATION
GLUTAMATE-RECEPTOR-6 GENE
SEROTONIN TRANSPORTER
SUSCEPTIBILITY LOCUS
GRIK2 POLYMORPHISMS
GENOMEWIDE SCREEN
INFANTILE-AUTISM
COMPLEX TRAITS
IDENTIFICATION

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Holt, R., Barnby, G., Maestrini, E., Bacchelli, E., Brocklebank, D., Sousa, I., Mulder, E., Kantojarvi, K., Jarvela, I., Klauck, S. M., Poustka, F., Bailey, A. J., van Engeland, H., de Jonge, M. V., et al., X., & Monaco, A. P. (2010). Linkage and candidate gene studies of autism spectrum disorders in European populations. European Journal of Human Genetics, 18(9), 1013-1019. https://doi.org/10.1038/ejhg.2010.69

@article{8e8bfacbc9c34a9bae1c4d3ec32ddad3,

title = "Linkage and candidate gene studies of autism spectrum disorders in European populations",

abstract = "Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 x 10(-5)) and between SND1 and strict autism (rs1881084, P=7.76 x 10(-5)) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1. European Journal of Human Genetics (2010) 18, 1013-1019; doi:10.1038/ejhg.2010.69; published online 5 May 2010",

keywords = "autistic disorder, linkage, association, candidate gene, PERVASIVE DEVELOPMENTAL DISORDERS, FAMILY-BASED ASSOCIATION, GLUTAMATE-RECEPTOR-6 GENE, SEROTONIN TRANSPORTER, SUSCEPTIBILITY LOCUS, GRIK2 POLYMORPHISMS, GENOMEWIDE SCREEN, INFANTILE-AUTISM, COMPLEX TRAITS, IDENTIFICATION",

author = "R. Holt and G. Barnby and E. Maestrini and E. Bacchelli and D. Brocklebank and I. Sousa and E. Mulder and K. Kantojarvi and I. Jarvela and S.M. Klauck and F Poustka and A.J. Bailey and {van Engeland}, H. and {de Jonge}, M.V. and {et al.}, X and A.P. Monaco",

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Holt, R, Barnby, G, Maestrini, E, Bacchelli, E, Brocklebank, D, Sousa, I, Mulder, E, Kantojarvi, K, Jarvela, I, Klauck, SM, Poustka, F, Bailey, AJ, van Engeland, H, de Jonge, MV, et al., X & Monaco, AP 2010, 'Linkage and candidate gene studies of autism spectrum disorders in European populations', European Journal of Human Genetics, vol. 18, no. 9, pp. 1013-1019. https://doi.org/10.1038/ejhg.2010.69

TY - JOUR

T1 - Linkage and candidate gene studies of autism spectrum disorders in European populations

AU - Holt, R.

AU - Barnby, G.

AU - Maestrini, E.

AU - Bacchelli, E.

AU - Brocklebank, D.

AU - Sousa, I.

AU - Mulder, E.

AU - Kantojarvi, K.

AU - Jarvela, I.

AU - Klauck, S.M.

AU - Poustka, F

AU - Bailey, A.J.

AU - van Engeland, H.

AU - de Jonge, M.V.

AU - et al., X

AU - Monaco, A.P.

PY - 2010/9/10

Y1 - 2010/9/10

N2 - Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 x 10(-5)) and between SND1 and strict autism (rs1881084, P=7.76 x 10(-5)) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1. European Journal of Human Genetics (2010) 18, 1013-1019; doi:10.1038/ejhg.2010.69; published online 5 May 2010

AB - Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 x 10(-5)) and between SND1 and strict autism (rs1881084, P=7.76 x 10(-5)) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1. European Journal of Human Genetics (2010) 18, 1013-1019; doi:10.1038/ejhg.2010.69; published online 5 May 2010

KW - autistic disorder

KW - linkage

KW - association

KW - candidate gene

KW - PERVASIVE DEVELOPMENTAL DISORDERS

KW - FAMILY-BASED ASSOCIATION

KW - GLUTAMATE-RECEPTOR-6 GENE

KW - SEROTONIN TRANSPORTER

KW - SUSCEPTIBILITY LOCUS

KW - GRIK2 POLYMORPHISMS

KW - GENOMEWIDE SCREEN

KW - INFANTILE-AUTISM

KW - COMPLEX TRAITS

KW - IDENTIFICATION

U2 - 10.1038/ejhg.2010.69

DO - 10.1038/ejhg.2010.69

M3 - Article

C2 - 20442744

SN - 1018-4813

VL - 18

SP - 1013

EP - 1019

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 9

ER -

Linkage and candidate gene studies of autism spectrum disorders in European populations

Abstract

Keywords

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