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PMID: 19734545 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Twin Study

A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.

Human molecular genetics ·Vol. 18 ·No. 23 ·2009-12-01 ·Pages 4650-61

Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KL, Hunt P, Ge D, Heinzen EL, Maia JM, Shianna KV, Weale ME, Cherkas LF, Clement G, Spector TD, Gibson G, Goldstein DB

Abstract

Psychiatric disorders such as schizophrenia are commonly accompanied by cognitive impairments that are treatment resistant and crucial to functional outcome. There has been great interest in studying cognitive measures as endophenotypes for psychiatric disorders, with the hope that their genetic basis will be clearer. To investigate this, we performed a genome-wide association study involving 11 cognitive phenotypes from the Cambridge Neuropsychological Test Automated Battery. We showed these measures to be heritable by comparing the correlation in 100 monozygotic and 100 dizygotic twin pairs. The full battery was tested in approximately 750 subjects, and for spatial and verbal recognition memory, we investigated a further 500 individuals to search for smaller genetic effects. We were unable to find any genome-wide significant associations with either SNPs or common copy number variants. Nor could we formally replicate any polymorphism that has been previously associated with cognition, although we found a weak signal of lower than expected P-values for variants in a set of 10 candidate genes. We additionally investigated SNPs in genomic loci that have been shown to harbor rare variants that associate with neuropsychiatric disorders, to see if they showed any suggestion of association when considered as a separate set. Only NRXN1 showed evidence of significant association with cognition. These results suggest that common genetic variation does not strongly influence cognition in healthy subjects and that cognitive measures do not represent a more tractable genetic trait than clinical endpoints such as schizophrenia. We discuss a possible role for rare variation in cognitive genomics.

MeSH Terms
Adolescent Adult Aged Calcium-Binding Proteins Cell Adhesion Molecules, Neuronal Cognition DNA Copy Number Variations Female Genetics, Population Genome-Wide Association Study Humans Male Middle Aged Nerve Tissue Proteins/genetics Neural Cell Adhesion Molecules Neuropsychological Tests Polymorphism, Single Nucleotide Twins/genetics,psychology Young Adult
Chemicals
Calcium-Binding Proteins Cell Adhesion Molecules, Neuronal NRXN1 protein, human Nerve Tissue Proteins Neural Cell Adhesion Molecules
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Need Anna C
Center for Human Genome Variation, Institute for Genome Sciences and Policy, Duke University, 450 Research Drive, Box 91009, Durham, NC 27708, USA.
Attix Deborah K
McEvoy Jill M
Cirulli Elizabeth T
Linney Kristen L
Hunt Priscilla
Ge Dongliang
Heinzen Erin L
Maia Jessica M
Shianna Kevin V
Weale Michael E
Cherkas Lynn F
Clement Gail
Spector Tim D
Gibson Greg
Goldstein David B
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Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
ISSN
1460-2083
DOI
10.1093/hmg/ddp413
Published
2009-12-01
Epub
2009-00-04
Pages
4650-61
Language
English
Region
England
NLM ID
9208958
PMCID
PMC2773267
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · G20234 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1093/hmg/ddp413 PMC Full Text View journal details
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