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 co-morbidity 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.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom. andrew.macleod@ed.ac.uk
authors.forename: Andrew K
authors.initials: AK
authors.lastname: MacLeod
authors.forename: Gail
authors.initials: G
authors.lastname: Davies
authors.forename: Antony
authors.initials: A
authors.lastname: Payton
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: David
authors.initials: D
authors.lastname: Liewald
authors.forename: Xiayi
authors.initials: X
authors.lastname: Ke
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Lopez
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Gow
authors.forename: Janie
authors.initials: J
authors.lastname: Corley
authors.forename: Paul
authors.initials: P
authors.lastname: Redmond
authors.forename: Geraldine
authors.initials: G
authors.lastname: McNeill
authors.forename: Andrew
authors.initials: A
authors.lastname: Pickles
authors.forename: William
authors.initials: W
authors.lastname: Ollier
authors.forename: Michael
authors.initials: M
authors.lastname: Horan
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.forename: Pippa A
authors.initials: PA
authors.lastname: Thomson
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics*; D000465:Algorithms; D003071:Cognition / Q000502:physiology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D006801:Humans; D007360:Intelligence; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype
chemical_list: D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human