title: Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences.
abstract: Two themes are emerging regarding the molecular genetic aetiology of intelligence. The first is that intelligence is influenced by many variants and those that are tagged by common single nucleotide polymorphisms account for around 30% of the phenotypic variation. The second, in line with other polygenic traits such as height and schizophrenia, is that these variants are not randomly distributed across the genome but cluster in genes that work together. Less clear is whether the very low range of cognitive ability (intellectual disability) is simply one end of the normal distribution describing individual differences in cognitive ability across a population. Here, we examined 40 genes with a known association with non-syndromic autosomal recessive intellectual disability (NS-ARID) to determine if they are enriched for common variants associated with the normal range of intelligence differences. The current study used the 3511 individuals of the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium. In addition, a text mining analysis was used to identify gene sets biologically related to the NS-ARID set. Gene-based tests indicated that genes implicated in NS-ARID were not significantly enriched for quantitative trait loci (QTL) associated with intelligence. These findings suggest that genes in which mutations can have a large and deleterious effect on intelligence are not associated with variation across the range of intelligence differences.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: W D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Liewald
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Payton
authors.affiliation: Aberdeen Biomedical Imaging Centre, University of Aberdeen, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: McNeil
authors.affiliation: Aberdeen Biomedical Imaging Centre, University of Aberdeen, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Whalley
authors.affiliation: Centre for Clinical and Cognitive Neurosciences, Institute Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Horan
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
authors.forename: W
authors.initials: W
authors.lastname: Ollier
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Starr
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
authors.forename: N
authors.initials: N
authors.lastname: Pendleton
authors.affiliation: QIMR, Berghofer Medical Research Institution, Brisbane, Australia.
authors.forename: N K
authors.initials: NK
authors.lastname: Hansel
authors.affiliation: QIMR, Berghofer Medical Research Institution, Brisbane, Australia.
authors.forename: G W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: QIMR, Berghofer Medical Research Institution, Brisbane, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: QIMR, Berghofer Medical Research Institution, Brisbane, Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: QIMR, Berghofer Medical Research Institution, Brisbane, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: T C
authors.initials: TC
authors.lastname: Bates
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
keywords: GWAS; Gene set analysis; Genetics; Intellectual disabilities