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

T.S. Rizzi, A. Arias-Vasquez, N. Rommelse, J. Kuntsi, R. Anney, P. Asherson, J. Buitelaar, T. Banaschewski, R. Ebstein, D. Ruano, S. van der Sluis, C.A. Markunas, M.E. Garrett, A.E. Ashley-Koch, S.H. Kollins, A.D. Anastopoulos, N.K. Hnasell, M.J. Wright, G.W. Montgomery, N.G. Martin & 23 others S.E. Harris, G. Davies, A. Tenesa, D.J. Porteous, J.M. Starr, I.J. Deary, B. St Pourcain, G. Davey Smith, N.J. Timpson, D.M. Evans, M. Gill, A. Miranda, F. Mulas, R.D. Oades, H. Roeyers, A. Rothenberger, J.A. Sergeant, E. Sonuga-Barke, H.C. Steinhausen, E. Taylor, S.V. Faraone, B. Franke, D. Posthuma

Research output: Contribution to JournalArticleAcademicpeer-review

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. © 2010 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)145-157
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume156
Issue number2
DOIs
Publication statusPublished - 2011

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Attention Deficit Disorder with Hyperactivity
Intelligence
Single Nucleotide Polymorphism
Genes
Genome
Chromosome Mapping
Genome-Wide Association Study
Computer Simulation
Psychiatry
Growth
Population

Cite this

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. ; Hnasell, N.K. ; Wright, M.J. ; Montgomery, G.W. ; Martin, N.G. ; Harris, S.E. ; Davies, G. ; Tenesa, A. ; Porteous, D.J. ; Starr, J.M. ; Deary, I.J. ; St Pourcain, B. ; Davey Smith, G. ; Timpson, N.J. ; Evans, D.M. ; Gill, M. ; Miranda, A. ; Mulas, F. ; Oades, R.D. ; Roeyers, H. ; Rothenberger, A. ; Sergeant, J.A. ; Sonuga-Barke, E. ; Steinhausen, H.C. ; Taylor, E. ; Faraone, S.V. ; Franke, B. ; Posthuma, D. / The ATXN1 and TRIM31 Genes Are Related to Intelligence in an ADHD Background: Evidence From a Large Collaborative Study Totaling 4,963 Subjects. In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2011 ; Vol. 156, No. 2. pp. 145-157.
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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. {\circledC} 2010 Wiley-Liss, Inc.",
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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, Hnasell, NK, Wright, MJ, Montgomery, GW, Martin, NG, Harris, SE, Davies, G, Tenesa, A, Porteous, DJ, Starr, JM, Deary, IJ, St Pourcain, B, Davey Smith, G, Timpson, NJ, Evans, DM, Gill, M, Miranda, A, Mulas, F, Oades, RD, Roeyers, H, Rothenberger, A, Sergeant, JA, 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. 156, 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, 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.; Hnasell, N.K.; Wright, M.J.; Montgomery, G.W.; Martin, N.G.; Harris, S.E.; Davies, G.; Tenesa, A.; Porteous, D.J.; Starr, J.M.; Deary, I.J.; St Pourcain, B.; Davey Smith, G.; Timpson, N.J.; Evans, D.M.; Gill, M.; Miranda, A.; Mulas, F.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.; Steinhausen, H.C.; Taylor, E.; Faraone, S.V.; Franke, B.; Posthuma, D.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 156, No. 2, 2011, p. 145-157.

Research output: Contribution to JournalArticleAcademicpeer-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, T.S.

AU - Arias-Vasquez, A.

AU - Rommelse, N.

AU - Kuntsi, J.

AU - Anney, R.

AU - Asherson, P.

AU - Buitelaar, J.

AU - Banaschewski, T.

AU - Ebstein, R.

AU - Ruano, D.

AU - van der Sluis, S.

AU - Markunas, C.A.

AU - Garrett, M.E.

AU - Ashley-Koch, A.E.

AU - Kollins, S.H.

AU - Anastopoulos, A.D.

AU - Hnasell, N.K.

AU - Wright, M.J.

AU - Montgomery, G.W.

AU - Martin, N.G.

AU - Harris, S.E.

AU - Davies, G.

AU - Tenesa, A.

AU - Porteous, D.J.

AU - Starr, J.M.

AU - Deary, I.J.

AU - St Pourcain, B.

AU - Davey Smith, G.

AU - Timpson, N.J.

AU - Evans, D.M.

AU - Gill, M.

AU - Miranda, A.

AU - Mulas, F.

AU - Oades, R.D.

AU - Roeyers, H.

AU - Rothenberger, A.

AU - Sergeant, J.A.

AU - Sonuga-Barke, E.

AU - Steinhausen, H.C.

AU - Taylor, E.

AU - Faraone, S.V.

AU - Franke, B.

AU - Posthuma, D.

PY - 2011

Y1 - 2011

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. © 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. © 2010 Wiley-Liss, Inc.

U2 - 10.1002/ajmg.b.31149

DO - 10.1002/ajmg.b.31149

M3 - Article

VL - 156

SP - 145

EP - 157

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

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

SN - 1552-4841

IS - 2

ER -