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.
Highlights
Intelligence is a highly heritable complex trait, for which it is hypothesized that many genes of small effect size contribute to its variability [McClearn et al, 1997; Plomin, 1999]
When combining the two samples ascertained for attention deficit/hyperactivity disorder (ADHD) we found that of all tested single nucleotide polymorphisms (SNPs), 12 had a P-value
As available samples differed in ascertainment method we tested for SNP associations with intelligence quotient test (IQ) in an ADHD background and in a non -ADHD, general population, background
Summary
Intelligence is a highly heritable complex trait, for which it is hypothesized that many genes of small effect size contribute to its variability [McClearn et al, 1997; Plomin, 1999]. Plomin and coworkers [Plomin, 1999; Plomin et al, 2001, 2004; Butcher et al, 2005, 2008] conducted several genome wide association (GWA) studies and showed significant association of a RIZZI ET AL. The region on chromosome 6 (6p2521.2) overlaps with the locus (6p24.1) identified in the genomewide association study performed by Butcher et al [2008]. Converging evidence from these whole genome studies provides support for the involvement of six different chromosomal regions, 2q24.1-31.1, 2q31.3, 6p25-21.2, 7q32.1, 14q11.2-12, and 16p13.3, in human intelligence (see Table I)
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Schedule a callMore From: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
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