Genetic Copy Number Variation and General Cognitive Ability

Andrew K. MacLeod; Gail Davies; Antony Payton; Albert Tenesa; Sarah E. Harris; David Liewald; Xiayi Ke; Michelle Luciano; Lorna M. Lopez; Alan J. Gow; Janie Corley; Paul Redmond; Geraldine McNeill; Andrew Pickles; William Ollier; Michael Horan; John M. Starr; Neil Pendleton; Pippa A. Thomson; David J. Porteous; Ian J. Deary

doi:10.1371/journal.pone.0037385

Genetic Copy Number Variation and General Cognitive Ability

Andrew K. MacLeod^*, Gail Davies, Antony Payton, Albert Tenesa, Sarah E. Harris, David Liewald, Xiayi Ke, Michelle Luciano, Lorna M. Lopez, Alan J. Gow, Janie Corley, Paul Redmond, Geraldine McNeill, Andrew Pickles, William Ollier, Michael Horan, John M. Starr, Neil Pendleton, Pippa A. Thomson, David J. PorteousIan J. Deary

^*Corresponding author for this work

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

18 Citations (Scopus)

Abstract

Differences in genomic structure between individuals are ubiquitous features of human genetic variation. Specific copy number variants (CNVs) have been associated with susceptibility to numerous complex psychiatric disorders, including attention-deficit-hyperactivity disorder, autism-spectrum disorders and schizophrenia. These disorders often display comorbidity with low intelligence. Rare chromosomal deletions and duplications are associated with these disorders, so it has been suggested that these deletions or duplications may be associated with differences in intelligence. Here we investigate associations between large (>= 500kb), rare (<1% population frequency) CNVs and both fluid and crystallized intelligence in community-dwelling older people. We observe no significant associations between intelligence and total CNV load. Examining individual CNV regions previously implicated in neuropsychological disorders, we find suggestive evidence that CNV regions around SHANK3 are associated with fluid intelligence as derived from a battery of cognitive tests. This is the first study to examine the effects of rare CNVs as called by multiple algorithms on cognition in a large non-clinical sample, and finds no effects of such variants on general cognitive ability.

Original language	English
Article number	37385
Number of pages	9
Journal	PL o S One
Volume	7
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0037385
Publication status	Published - 26 Dec 2012

Keywords

RARE CHROMOSOMAL DELETIONS
AUTISM SPECTRUM DISORDER
HIDDEN-MARKOV MODEL
SNP GENOTYPING DATA
GENOME-WIDE
MISSING HERITABILITY
MENTAL-RETARDATION
HUMAN INTELLIGENCE
STRUCTURAL VARIATION
PARKINSONS-DISEASE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0037385Licence: CC BY

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MacLeod, A. K., Davies, G., Payton, A., Tenesa, A., Harris, S. E., Liewald, D., Ke, X., Luciano, M., Lopez, L. M., Gow, A. J., Corley, J., Redmond, P., McNeill, G., Pickles, A., Ollier, W., Horan, M., Starr, J. M., Pendleton, N., Thomson, P. A., ... Deary, I. J. (2012). Genetic Copy Number Variation and General Cognitive Ability. PL o S One , 7(12), Article 37385. https://doi.org/10.1371/journal.pone.0037385

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title = "Genetic Copy Number Variation and General Cognitive Ability",

abstract = "Differences in genomic structure between individuals are ubiquitous features of human genetic variation. Specific copy number variants (CNVs) have been associated with susceptibility to numerous complex psychiatric disorders, including attention-deficit-hyperactivity disorder, autism-spectrum disorders and schizophrenia. These disorders often display comorbidity with low intelligence. Rare chromosomal deletions and duplications are associated with these disorders, so it has been suggested that these deletions or duplications may be associated with differences in intelligence. Here we investigate associations between large (>= 500kb), rare (<1% population frequency) CNVs and both fluid and crystallized intelligence in community-dwelling older people. We observe no significant associations between intelligence and total CNV load. Examining individual CNV regions previously implicated in neuropsychological disorders, we find suggestive evidence that CNV regions around SHANK3 are associated with fluid intelligence as derived from a battery of cognitive tests. This is the first study to examine the effects of rare CNVs as called by multiple algorithms on cognition in a large non-clinical sample, and finds no effects of such variants on general cognitive ability.",

keywords = "RARE CHROMOSOMAL DELETIONS, AUTISM SPECTRUM DISORDER, HIDDEN-MARKOV MODEL, SNP GENOTYPING DATA, GENOME-WIDE, MISSING HERITABILITY, MENTAL-RETARDATION, HUMAN INTELLIGENCE, STRUCTURAL VARIATION, PARKINSONS-DISEASE",

author = "MacLeod, {Andrew K.} and Gail Davies and Antony Payton and Albert Tenesa and Harris, {Sarah E.} and David Liewald and Xiayi Ke and Michelle Luciano and Lopez, {Lorna M.} and Gow, {Alan J.} and Janie Corley and Paul Redmond and Geraldine McNeill and Andrew Pickles and William Ollier and Michael Horan and Starr, {John M.} and Neil Pendleton and Thomson, {Pippa A.} and Porteous, {David J.} and Deary, {Ian J.}",

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MacLeod, AK, Davies, G, Payton, A, Tenesa, A, Harris, SE, Liewald, D, Ke, X, Luciano, M, Lopez, LM, Gow, AJ, Corley, J, Redmond, P, McNeill, G, Pickles, A, Ollier, W, Horan, M, Starr, JM, Pendleton, N, Thomson, PA, Porteous, DJ & Deary, IJ 2012, 'Genetic Copy Number Variation and General Cognitive Ability', PL o S One , vol. 7, no. 12, 37385. https://doi.org/10.1371/journal.pone.0037385

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T1 - Genetic Copy Number Variation and General Cognitive Ability

AU - MacLeod, Andrew K.

AU - Davies, Gail

AU - Payton, Antony

AU - Tenesa, Albert

AU - Harris, Sarah E.

AU - Liewald, David

AU - Ke, Xiayi

AU - Luciano, Michelle

AU - Lopez, Lorna M.

AU - Gow, Alan J.

AU - Corley, Janie

AU - Redmond, Paul

AU - McNeill, Geraldine

AU - Pickles, Andrew

AU - Ollier, William

AU - Horan, Michael

AU - Starr, John M.

AU - Pendleton, Neil

AU - Thomson, Pippa A.

AU - Porteous, David J.

AU - Deary, Ian J.

PY - 2012/12/26

Y1 - 2012/12/26

N2 - Differences in genomic structure between individuals are ubiquitous features of human genetic variation. Specific copy number variants (CNVs) have been associated with susceptibility to numerous complex psychiatric disorders, including attention-deficit-hyperactivity disorder, autism-spectrum disorders and schizophrenia. These disorders often display comorbidity with low intelligence. Rare chromosomal deletions and duplications are associated with these disorders, so it has been suggested that these deletions or duplications may be associated with differences in intelligence. Here we investigate associations between large (>= 500kb), rare (<1% population frequency) CNVs and both fluid and crystallized intelligence in community-dwelling older people. We observe no significant associations between intelligence and total CNV load. Examining individual CNV regions previously implicated in neuropsychological disorders, we find suggestive evidence that CNV regions around SHANK3 are associated with fluid intelligence as derived from a battery of cognitive tests. This is the first study to examine the effects of rare CNVs as called by multiple algorithms on cognition in a large non-clinical sample, and finds no effects of such variants on general cognitive ability.

AB - Differences in genomic structure between individuals are ubiquitous features of human genetic variation. Specific copy number variants (CNVs) have been associated with susceptibility to numerous complex psychiatric disorders, including attention-deficit-hyperactivity disorder, autism-spectrum disorders and schizophrenia. These disorders often display comorbidity with low intelligence. Rare chromosomal deletions and duplications are associated with these disorders, so it has been suggested that these deletions or duplications may be associated with differences in intelligence. Here we investigate associations between large (>= 500kb), rare (<1% population frequency) CNVs and both fluid and crystallized intelligence in community-dwelling older people. We observe no significant associations between intelligence and total CNV load. Examining individual CNV regions previously implicated in neuropsychological disorders, we find suggestive evidence that CNV regions around SHANK3 are associated with fluid intelligence as derived from a battery of cognitive tests. This is the first study to examine the effects of rare CNVs as called by multiple algorithms on cognition in a large non-clinical sample, and finds no effects of such variants on general cognitive ability.

KW - RARE CHROMOSOMAL DELETIONS

KW - AUTISM SPECTRUM DISORDER

KW - HIDDEN-MARKOV MODEL

KW - SNP GENOTYPING DATA

KW - GENOME-WIDE

KW - MISSING HERITABILITY

KW - MENTAL-RETARDATION

KW - HUMAN INTELLIGENCE

KW - STRUCTURAL VARIATION

KW - PARKINSONS-DISEASE

U2 - 10.1371/journal.pone.0037385

DO - 10.1371/journal.pone.0037385

M3 - Article

SN - 1932-6203

VL - 7

JO - PL o S One

JF - PL o S One

IS - 12

M1 - 37385

ER -

Genetic Copy Number Variation and General Cognitive Ability

Abstract

Keywords

UN SDGs

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