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The ATXN1 and TRIM31 genes are related to intelligence in an ADHD background: Evidence from a large collaborative study totaling 4963 subjects. American Journal of Medical Genetics Part B, 156, 145-157. (doi 10.1002/ajmg.b.31149). view article - [Request a copy]

Introduction: Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, 5 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 datasets 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. .

Methods: 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, & to attempt replication of previously reported candidate genes for intelligence.

Results:
1 - Although this sample was ascertained for ADHD, IQ scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in 5 genomic loci previously identified through whole genome linkage and association analyses.

2 - Significant SNPs were tested in 4 independent samples (4357 subjects), one ascertained for ADHD and 3 population based samples.

3 - Associations between intelligence & SNPs in the ATXN1 (ataxin 1) and TRIM31 (tripartite motif-containing 31) genes and in 3 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.

Background: ATXN1 is present in the nucleus of the neurons of the basal ganglia, pons and cortex, and in both cytoplasm and nucleus of Purkinje cells of the cerebellum [Servadio et al. 1995] (previously called SCA1 gene due to the association with spinocerebellar ataxia-1, SCA1). Mice lacking ATXN1 are characterized by decreased exploratory behavior, pronounced deficits in the spatial performance on the rotating rod apparatus [Matilla et al. 1998], pointing to the possible role of ATXN1 in learning and memory. Other members of the TRIM family (TRIM3, MIM: 605493) were reported to modulate NGF-induced neurite outgrowth in PC12 cells [El-Husseini and Vincent, 1999].