A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
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.
Need
Anna C
AC
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
DK
McEvoy
Jill M
JM
Cirulli
Elizabeth T
ET
Linney
Kristen L
KL
Hunt
Priscilla
P
Ge
Dongliang
D
Heinzen
Erin L
EL
Maia
Jessica M
JM
Shianna
Kevin V
KV
Weale
Michael E
ME
Cherkas
Lynn F
LF
Clement
Gail
G
Spector
Tim D
TD
Gibson
Greg
G
Goldstein
David B
DB
D000293:Adolescent; D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D003071:Cognition; D056915:DNA Copy Number Variations; D005260:Female; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D014427:Twins / Q000235:genetics* / Q000523:psychology; D055815:Young Adult
D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules