Exome sequencing to detect rare variants associated with general cognitive ability: A pilot study

Luciano, Michelle, Svinti, Victoria, Campbell, Archie, Marioni, Riccardo E., Hayward, Caroline, Wright, Alan F., Taylor, Martin S., Porteous, David J., Thomson, Pippa, Prendergast, James G. D., Hastie, Nicholas D., Farrington, Susan M., Scotland, Generation, Dunlop, Malcolm G. and Deary, Ian J. (2015) Exome sequencing to detect rare variants associated with general cognitive ability: A pilot study. Twin Research and Human Genetics, 18 2: 117-125. doi:10.1017/thg.2015.10

Author Luciano, Michelle
Svinti, Victoria
Campbell, Archie
Marioni, Riccardo E.
Hayward, Caroline
Wright, Alan F.
Taylor, Martin S.
Porteous, David J.
Thomson, Pippa
Prendergast, James G. D.
Hastie, Nicholas D.
Farrington, Susan M.
Scotland, Generation
Dunlop, Malcolm G.
Deary, Ian J.
Title Exome sequencing to detect rare variants associated with general cognitive ability: A pilot study
Journal name Twin Research and Human Genetics   Check publisher's open access policy
ISSN 1832-4274
Publication date 2015-04-25
Year available 2015
Sub-type Article (original research)
DOI 10.1017/thg.2015.10
Volume 18
Issue 2
Start page 117
End page 125
Total pages 9
Place of publication Cambridge, United Kingdom
Publisher Cambridge University Press
Collection year 2016
Language eng
Formatted abstract
Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.
Keyword Generation Scotland: the Scottish family health study
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
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