The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects

Thais S. Rizzi; Alejandro Arias-Vasquez; Nanda Rommelse; Jonna Kuntsi; Richard Anney; Philip Asherson; Jan Buitelaar; Tobias Banaschewski; Richard Ebstein; Dina Ruano; Sophie Van der Sluis; Christina A. Markunas; Melanie E. Garrett; Allison E. Ashley-Koch; Scott H. Kollins; Arthur D. Anastopoulos; Narelle K. Hansell; Margaret J. Wright; Grant W. Montgomery; Nicholas G. Martin; Sarah E. Harris; Gail Davies; Albert Tenesa; David J. Porteous; John M. Starr; Ian J. Deary; Beate St Pourcain; George Davey Smith; Nicholas J. Timpson; David M. Evans; Michael Gill; Ana Miranda; Fernando Mulas; Robert D. Oades; Herbert Roeyers; Aribert Rothenberger; Joseph Sergeant; Edmund Sonuga-Barke; Hans Christoph Steinhausen; Eric Taylor; Stephen V. Faraone; Barbara Franke; Danielle Posthuma

doi:10.1002/ajmg.b.31149

The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects

Thais S. Rizzi, Alejandro Arias-Vasquez, Nanda Rommelse, Jonna Kuntsi, Richard Anney, Philip Asherson, Jan Buitelaar, Tobias Banaschewski, Richard Ebstein, Dina Ruano, Sophie Van der Sluis, Christina A. Markunas, Melanie E. Garrett, Allison E. Ashley-Koch, Scott H. Kollins, Arthur D. Anastopoulos, Narelle K. Hansell, Margaret J. Wright, Grant W. Montgomery, Nicholas G. MartinSarah E. Harris, Gail Davies, Albert Tenesa, David J. Porteous, John M. Starr, Ian J. Deary, Beate St Pourcain, George Davey Smith, Nicholas J. Timpson, David M. Evans, Michael Gill, Ana Miranda, Fernando Mulas, Robert D. Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Edmund Sonuga-Barke, Hans Christoph Steinhausen, Eric Taylor, Stephen V. Faraone, Barbara Franke, Danielle Posthuma

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22 Citations (Scopus)

Abstract

Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder. (C) 2010 Wiley-Liss, Inc.

Original language	English
Pages (from-to)	145 - 157
Number of pages	13
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	156B
Issue number	2
DOIs	https://doi.org/10.1002/ajmg.b.31149
Publication status	Published - Mar 2011

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Rizzi, T. S., Arias-Vasquez, A., Rommelse, N., Kuntsi, J., Anney, R., Asherson, P., Buitelaar, J., Banaschewski, T., Ebstein, R., Ruano, D., Van der Sluis, S., Markunas, C. A., Garrett, M. E., Ashley-Koch, A. E., Kollins, S. H., Anastopoulos, A. D., Hansell, N. K., Wright, M. J., Montgomery, G. W., ... Posthuma, D. (2011). The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 156B(2), 145 - 157. https://doi.org/10.1002/ajmg.b.31149

@article{9fcbeb0a50144238994f2a4f32c905a0,

title = "The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects",

abstract = "Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder. (C) 2010 Wiley-Liss, Inc.",

author = "Rizzi, {Thais S.} and Alejandro Arias-Vasquez and Nanda Rommelse and Jonna Kuntsi and Richard Anney and Philip Asherson and Jan Buitelaar and Tobias Banaschewski and Richard Ebstein and Dina Ruano and {Van der Sluis}, Sophie and Markunas, {Christina A.} and Garrett, {Melanie E.} and Ashley-Koch, {Allison E.} and Kollins, {Scott H.} and Anastopoulos, {Arthur D.} and Hansell, {Narelle K.} and Wright, {Margaret J.} and Montgomery, {Grant W.} and Martin, {Nicholas G.} and Harris, {Sarah E.} and Gail Davies and Albert Tenesa and Porteous, {David J.} and Starr, {John M.} and Deary, {Ian J.} and {St Pourcain}, Beate and Smith, {George Davey} and Timpson, {Nicholas J.} and Evans, {David M.} and Michael Gill and Ana Miranda and Fernando Mulas and Oades, {Robert D.} and Herbert Roeyers and Aribert Rothenberger and Joseph Sergeant and Edmund Sonuga-Barke and Steinhausen, {Hans Christoph} and Eric Taylor and Faraone, {Stephen V.} and Barbara Franke and Danielle Posthuma",

year = "2011",

month = mar,

doi = "10.1002/ajmg.b.31149",

language = "English",

volume = "156B",

pages = "145 -- 157",

journal = "American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics",

issn = "1552-485X",

publisher = "Wiley-Liss Inc.",

number = "2",

}

Rizzi, TS, Arias-Vasquez, A, Rommelse, N, Kuntsi, J, Anney, R, Asherson, P, Buitelaar, J, Banaschewski, T, Ebstein, R, Ruano, D, Van der Sluis, S, Markunas, CA, Garrett, ME, Ashley-Koch, AE, Kollins, SH, Anastopoulos, AD, Hansell, NK, Wright, MJ, Montgomery, GW, Martin, NG, Harris, SE, Davies, G, Tenesa, A, Porteous, DJ, Starr, JM, Deary, IJ, St Pourcain, B, Smith, GD, Timpson, NJ, Evans, DM, Gill, M, Miranda, A, Mulas, F, Oades, RD, Roeyers, H, Rothenberger, A, Sergeant, J, Sonuga-Barke, E, Steinhausen, HC, Taylor, E, Faraone, SV, Franke, B & Posthuma, D 2011, 'The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 156B, no. 2, pp. 145 - 157. https://doi.org/10.1002/ajmg.b.31149

The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects. / Rizzi, Thais S.; Arias-Vasquez, Alejandro; Rommelse, Nanda et al.
In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 156B, No. 2, 03.2011, p. 145 - 157.

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

TY - JOUR

T1 - The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects

AU - Rizzi, Thais S.

AU - Arias-Vasquez, Alejandro

AU - Rommelse, Nanda

AU - Kuntsi, Jonna

AU - Anney, Richard

AU - Asherson, Philip

AU - Buitelaar, Jan

AU - Banaschewski, Tobias

AU - Ebstein, Richard

AU - Ruano, Dina

AU - Van der Sluis, Sophie

AU - Markunas, Christina A.

AU - Garrett, Melanie E.

AU - Ashley-Koch, Allison E.

AU - Kollins, Scott H.

AU - Anastopoulos, Arthur D.

AU - Hansell, Narelle K.

AU - Wright, Margaret J.

AU - Montgomery, Grant W.

AU - Martin, Nicholas G.

AU - Harris, Sarah E.

AU - Davies, Gail

AU - Tenesa, Albert

AU - Porteous, David J.

AU - Starr, John M.

AU - Deary, Ian J.

AU - St Pourcain, Beate

AU - Smith, George Davey

AU - Timpson, Nicholas J.

AU - Evans, David M.

AU - Gill, Michael

AU - Miranda, Ana

AU - Mulas, Fernando

AU - Oades, Robert D.

AU - Roeyers, Herbert

AU - Rothenberger, Aribert

AU - Sergeant, Joseph

AU - Sonuga-Barke, Edmund

AU - Steinhausen, Hans Christoph

AU - Taylor, Eric

AU - Faraone, Stephen V.

AU - Franke, Barbara

AU - Posthuma, Danielle

PY - 2011/3

Y1 - 2011/3

N2 - Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder. (C) 2010 Wiley-Liss, Inc.

AB - Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder. (C) 2010 Wiley-Liss, Inc.

U2 - 10.1002/ajmg.b.31149

DO - 10.1002/ajmg.b.31149

M3 - Article

SN - 1552-485X

VL - 156B

SP - 145

EP - 157

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

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

IS - 2

ER -

The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects

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