Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences

W David Hill; Gail Davies; David Liewald; A. Payton; C.j. Mcneil; L.j. Whalley; M. Horan; W. Ollier; John Starr; N. Pendleton; N.k. Hansel; G.w. Montgomery; S.e. Medland; N.g. Martin; M.j. Wright; T. C. Bates; Ian J Deary

doi:10.1016/j.intell.2015.11.005

Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences

W David Hill, Gail Davies, David Liewald, A. Payton, C.j. Mcneil, L.j. Whalley, M. Horan, W. Ollier, John Starr, N. Pendleton, N.k. Hansel, G.w. Montgomery, S.e. Medland, N.g. Martin, M.j. Wright, T. C. Bates, Ian J Deary

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	80-89
Journal	Intelligence
Volume	54
DOIs	https://doi.org/10.1016/j.intell.2015.11.005
Publication status	Published - 1 Jan 2016

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Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Maclullich, A. (Principal Investigator)
1/09/13 → 31/08/19
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I. (Principal Investigator), Gale, C. (Co-investigator), Holmes, M. (Co-investigator), Logie, P. (Co-investigator), Maclullich, A. (Co-investigator), Porteous, D. (Co-investigator), Seckl, J. (Co-investigator), Starr, J. (Co-investigator), Wardlaw, J. (Co-investigator) & Okely, J. (Researcher)
1/09/13 → 31/08/19
Project: Research
A genome wide association study of non pathological cognitive ageing
Deary, I. (Principal Investigator), Porteous, D. (Co-investigator) & Tenesa, A. (Co-investigator)
BBSRC
1/09/08 → 31/08/10
Project: Research

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Hill, W. D., Davies, G., Liewald, D., Payton, A., Mcneil, C. J., Whalley, L. J., Horan, M., Ollier, W., Starr, J., Pendleton, N., Hansel, N. K., Montgomery, G. W., Medland, S. E., Martin, N. G., Wright, M. J., Bates, T. C., & Deary, I. J. (2016). Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences. Intelligence, 54, 80-89. https://doi.org/10.1016/j.intell.2015.11.005

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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.",

author = "Hill, {W David} and Gail Davies and David Liewald and A. Payton and C.j. Mcneil and L.j. Whalley and M. Horan and W. Ollier and John Starr and N. Pendleton and N.k. Hansel and G.w. Montgomery and S.e. Medland and N.g. Martin and M.j. Wright and Bates, {T. C.} and Deary, {Ian J}",

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doi = "10.1016/j.intell.2015.11.005",

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Hill, WD , Davies, G, Liewald, D, Payton, A, Mcneil, CJ, Whalley, LJ, Horan, M, Ollier, W, Starr, J, Pendleton, N, Hansel, NK, Montgomery, GW, Medland, SE, Martin, NG, Wright, MJ, Bates, TC & Deary, IJ 2016, 'Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences', Intelligence, vol. 54, pp. 80-89. https://doi.org/10.1016/j.intell.2015.11.005

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AU - Hill, W David

AU - Davies, Gail

AU - Liewald, David

AU - Payton, A.

AU - Mcneil, C.j.

AU - Whalley, L.j.

AU - Horan, M.

AU - Ollier, W.

AU - Starr, John

AU - Pendleton, N.

AU - Hansel, N.k.

AU - Montgomery, G.w.

AU - Medland, S.e.

AU - Martin, N.g.

AU - Wright, M.j.

AU - Bates, T. C.

AU - Deary, Ian J

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N2 - 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.

AB - 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.

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DO - 10.1016/j.intell.2015.11.005

M3 - Article

SN - 0160-2896

VL - 54

SP - 80

EP - 89

JO - Intelligence

JF - Intelligence

ER -

Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences

Abstract

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Projects

Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A genome wide association study of non pathological cognitive ageing

Cite this