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Genetic Copy Number Variation and General Cognitive Ability
Authors: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
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.
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