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 - Davey Smith, George
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
N1 - Copyright © 2010 Wiley-Liss, Inc.
PY - 2011/3/1
Y1 - 2011/3/1
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.
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.
KW - Attention Deficit Disorder with Hyperactivity
KW - Cohort Studies
KW - European Continental Ancestry Group
KW - Humans
KW - Intelligence
KW - Meta-Analysis as Topic
KW - Nerve Tissue Proteins
KW - Nuclear Family
KW - Nuclear Proteins
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Ubiquitin-Protein Ligases
U2 - 10.1002/ajmg.b.31149
DO - 10.1002/ajmg.b.31149
M3 - Journal article
SN - 1552-4841
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
ER -