title: No effect of genome-wide copy number variation on measures of intelligence in a New Zealand birth cohort.
abstract: Variation in human intelligence is approximately 50% heritable, but understanding of the genes involved is limited. Several forms of genetic variation remain under-studied in relation to intelligence, one of which is copy number variation (CNV). Using single-nucleotide polymorphism (SNP) -based microarrays, we genotyped CNVs genome-wide in a birth cohort of 723 New Zealanders, and correlated them with four intelligence-related phenotypes. We found no significant association for any common CNV after false discovery correction, which is consistent with previous work. In contrast to a previous study, however, we found no effect on any cognitive measure of rare CNV burden, defined as total number of bases inserted or deleted in CNVs rarer than 5%. We discuss possible reasons for this failure to replicate, including interaction between CNV and aging in determining the effects of rare CNVs. While our results suggest that no CNV assayable by SNP chips contributes more than a very small amount to variation in human intelligence, it remains possible that common CNVs in segmental duplication arrays, which are not well covered by SNP chips, are important contributors.
authors: Department of Pathology, University of Otago, Christchurch, New Zealand. andrew.bagshaw@gmail.com
authors: Andrew T M
authors: AT
authors: Bagshaw
authors: L John
authors: LJ
authors: Horwood
authors: Youfang
authors: Y
authors: Liu
authors: David M
authors: DM
authors: Fergusson
authors: Patrick F
authors: PF
authors: Sullivan
authors: Martin A
authors: MA
authors: Kennedy
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D007361:Intelligence Tests; D046228:Microarray Analysis; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
references: Nature. 2008 Sep 11;455(7210):237-41
references: 18668038
references: Nat Genet. 2008 Oct;40(10):1166-74
references: 18776908
references: N Engl J Med. 2008 Oct 16;359(16):1685-99
references: 18784092
references: Hum Mol Genet. 2002 Aug 15;11(17):1987-95
references: 12165560
references: Nature. 2012 Jan 18;482(7384):212-5
references: 22258510
references: Science. 2004 Jul 23;305(5683):525-8
references: 15273396
references: Am J Hum Genet. 2009 Feb;84(2):148-61
references: 19166990
references: Acta Paediatr. 2012 Jan;101(1):85-91
references: 21767312
references: Am J Hum Genet. 2005 Aug;77(2):318-26
references: 16001363
references: Nat Genet. 2004 Sep;36(9):949-51
references: 15286789
references: J Am Acad Child Adolesc Psychiatry. 2010 Nov;49(11):1091-104
references: 20970697
references: Curr Opin Neurol. 2012 Apr;25(2):150-8
references: 22357217
references: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10584-9
references: 20489179
references: Science. 2007 Apr 20;316(5823):445-9
references: 17363630
references: Clin Genet. 2013 Jan;83(1):53-65
references: 22283495
references: PLoS One. 2011 Jan 26;6(1):e16339
references: 21298096
references: Lancet Neurol. 2006 Nov;5(11):907-8
references: 17086647
references: Behav Genet. 2006 Jan;36(1):65-76
references: 16341908
references: Nature. 2009 May 28;459(7246):569-73
references: 19404257
references: Nat Genet. 2008 Oct;40(10):1199-203
references: 18776910
references: Nature. 1997 Jul 31;388(6641):468-71
references: 9242404
references: Hum Genet. 2009 Jul;126(1):215-32
references: 19294424
references: Behav Genet. 2010 Nov;40(6):759-67
references: 20306291
references: Behav Genet. 2009 Jul;39(4):359-70
references: 19381794
references: Aust N Z J Psychiatry. 2001 Jun;35(3):287-96
references: 11437801
references: Br J Psychiatry. 2011 Nov;199(5):398-403
references: 22045946
references: Cell. 2012 Mar 16;148(6):1223-41
references: 22424231
references: Behav Genet. 2006 Jan;36(1):77-86
references: 16341907
references: Am J Hum Genet. 2006 Aug;79(2):275-90
references: 16826518
references: Nat Genet. 2006 Jan;38(1):86-92
references: 16468122
references: Mol Psychiatry. 2011 Oct;16(10):996-1005
references: 21826061
references: Behav Genet. 2006 Jan;36(1):45-55
references: 16341610
references: Genes Brain Behav. 2008 Jun;7(4):435-46
references: 18067574
references: Nat Genet. 2008 Dec;40(12):1466-71
references: 19029900
references: Dev Psychobiol. 2012 Jul;54(5):475-92
references: 22674524
references: Nature. 2010 Jul 15;466(7304):368-72
references: 20531469
references: Genome Res. 2007 Nov;17(11):1665-74
references: 17921354
references: Behav Genet. 2006 Jan;36(1):56-64
references: 16362232
references: Behav Genet. 2012 Mar;42(2):187-98
references: 21969232
references: PLoS Genet. 2006 May;2(5):e80
references: 16733552
references: Behav Genet. 2001 Nov;31(6):511-31
references: 11838530
references: Genetics. 2011 Feb;187(2):367-83
references: 21115973
references: Genome Res. 2007 Sep;17(9):1266-77
references: 17666543
references: Science. 2006 Sep 1;313(5791):1304-7
references: 16946073
references: Paediatr Perinat Epidemiol. 1989 Jul;3(3):302-25
references: 2671961
references: Nat Rev Neurosci. 2010 Mar;11(3):201-11
references: 20145623
references: Science. 2010 Oct 29;330(6004):641-6
references: 21030649
references: Cold Spring Harb Symp Quant Biol. 2009;74:375-82
references: 19850849
references: Hum Mol Genet. 2009 Dec 1;18(23):4650-61
references: 19734545
references: Mol Psychiatry. 2010 Nov;15(11):1112-20
references: 19488046