title: The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis.
abstract: The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR variants included in association studies render it unclear whether OXTR is truly associated with ASD, and, if so, which OXTR single-nucleotide polymorphisms (SNPs) are associated. Thus, a meta-analytic review of extant studies is needed to determine whether OXTR shows association with ASD, and to elucidate which specific SNPs have a significant effect on ASD. The current meta-analysis of 16 OXTR SNPs included 3941 individuals with ASD from 11 independent samples, although analyses of each individual SNP included a subset of this total. We found significant associations between ASD and the SNPs rs7632287, rs237887, rs2268491 and rs2254298. OXTR was also significantly associated with ASD in a gene-based test. The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.
authors.affiliation: Psychology Department, Emory University, Atlanta, GA, USA.
authors.forename: D
authors.initials: D
authors.lastname: LoParo
authors.affiliation: Psychology Department, Emory University, Atlanta, GA, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Waldman
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018045:Receptors, Oxytocin / Q000235:genetics*
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21437-41
references.pmid: 19934046
references.citation: BMJ. 1997 Sep 13;315(7109):629-34
references.pmid: 9310563
references.citation: Neuron. 2011 Jun 9;70(5):806-8
references.pmid: 21658575
references.citation: Hum Mol Genet. 2010 Oct 15;19(20):4072-82
references.pmid: 20663923
references.citation: Eur J Hum Genet. 2010 Sep;18(9):1045-53
references.pmid: 20442747
references.citation: Nature. 2012 Apr 04;485(7397):246-50
references.pmid: 22495309
references.citation: Arch Med Res. 2007 Jan;38(1):70-4
references.pmid: 17174726
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4389-94
references.pmid: 20160081
references.citation: Trends Neurosci. 2010 Feb;33(2):103-9
references.pmid: 20005580
references.citation: Nature. 2012 Apr 04;485(7397):242-5
references.pmid: 22495311
references.citation: Mol Psychiatry. 2005 Jun;10(6):563-71
references.pmid: 15558079
references.citation: Prog Brain Res. 2008;170:79-90
references.pmid: 18655874
references.citation: Ann Hum Genet. 2009 May;73(Pt 3):263-73
references.pmid: 19456320
references.citation: Eur Child Adolesc Psychiatry. 2010 Mar;19(3):169-78
references.pmid: 19941018
references.citation: Mol Psychiatry. 2008 Oct;13(10):980-8
references.pmid: 17893705
references.citation: Mol Psychiatry. 2006 Jan;11(1):37-46
references.pmid: 16205737
references.citation: Autism Res. 2009 Jun;2(3):157-77
references.pmid: 19598235
references.citation: J Autism Dev Disord. 2000 Jun;30(3):205-23
references.pmid: 11055457
references.citation: J Abnorm Child Psychol. 2008 May;36(4):591-9
references.pmid: 18188537
references.citation: Neurosci Lett. 2007 Apr 24;417(1):6-9
references.pmid: 17383819
references.citation: Biol Psychiatry. 1998 Feb 15;43(4):270-7
references.pmid: 9513736
references.citation: J Child Psychol Psychiatry. 2004 Jan;45(1):135-70
references.pmid: 14959806
references.citation: Prog Brain Res. 2008;170:337-50
references.pmid: 18655894
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19189-92
references.pmid: 22084107
references.citation: Neurosci Biobehav Rev. 2013 Sep;37(8):1485-92
references.pmid: 23665533
references.citation: Am J Hum Genet. 2011 May 13;88(5):586-98
references.pmid: 21565292
references.citation: Biol Psychiatry. 2008 May 15;63(10):911-6
references.pmid: 18207134
references.citation: J Autism Dev Disord. 1980 Mar;10(1):91-103
references.pmid: 6927682
references.citation: Clin Trials. 2007;4(3):245-53
references.pmid: 17715249
references.citation: PLoS One. 2010 Dec 31;5(12):e14480
references.pmid: 21217833
references.citation: Ann Neurol. 2007 Sep;62(3):243-50
references.pmid: 17696172
references.citation: Neuron. 2011 Jun 9;70(5):886-97
references.pmid: 21658582
references.citation: PLoS One. 2009 May 20;4(5):e5535
references.pmid: 19461999
references.citation: J Am Acad Child Adolesc Psychiatry. 2004 May;43(5):548-58
references.pmid: 15100561
references.citation: Biol Psychiatry. 2007 Mar 15;61(6):731-3
references.pmid: 17137561
references.citation: Nat Rev Neurosci. 2012 May 10;13(6):359
references.pmid: 22573024
references.citation: Soc Cogn Affect Neurosci. 2008 Jun;3(2):128-34
references.pmid: 19015103
references.citation: Nature. 2005 Jun 2;435(7042):673-6
references.pmid: 15931222
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):629-639
references.pmid: 19777562
references.citation: Biol Psychiatry. 2008 Jan 1;63(1):3-5
references.pmid: 17888410
references.citation: Mol Autism. 2011 Jan 19;2(1):1
references.pmid: 21247446
references.citation: Biol Psychiatry. 2005 Jul 1;58(1):74-7
references.pmid: 15992526
references.citation: Ann Neurol. 2006 Jan;59(1):145-55
references.pmid: 16288458
references.citation: Horm Behav. 2006 Nov;50(4):506-17
references.pmid: 16890230
references.citation: Endocrinology. 2008 Jul;149(7):3256-63
references.pmid: 18356275
references.citation: Biol Psychiatry. 2003 Dec 15;54(12):1389-98
references.pmid: 14675803
references.citation: Biol Psychiatry. 2001 Oct 15;50(8):609-13
references.pmid: 11690596
references.citation: Front Neuroendocrinol. 2004 Sep-Dec;25(3-4):150-76
references.pmid: 15589267
references.citation: Am J Psychiatry. 2010 Nov;167(11):1357-63
references.pmid: 20686188
references.citation: Front Psychol. 2011 Aug 25;2:200
references.pmid: 21904531
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: J Hum Genet. 2010 Mar;55(3):137-41
references.pmid: 20094064
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: Biol Psychiatry. 2012 Aug 1;72(3):175-81
references.pmid: 22336563
references.citation: Am J Hum Genet. 2011 Mar 11;88(3):283-93
references.pmid: 21397060
references.citation: Biol Psychiatry. 2010 Apr 1;67(7):692-4
references.pmid: 19897177
references.citation: Neurosci Lett. 2010 May 3;474(3):163-167
references.pmid: 20303388
references.citation: Biol Psychiatry. 2012 Mar 1;71(5):419-26
references.pmid: 22015110
references.citation: Int J Dev Neurosci. 2007 Apr;25(2):69-85
references.pmid: 17236739
references.citation: J Neurodev Disord. 2011 Jun;3(2):101-12
references.pmid: 21484202
references.citation: Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1987-92
references.pmid: 24367110
references.citation: Nature. 2012 Apr 04;485(7397):237-41
references.pmid: 22495306
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13936-41
references.pmid: 20647384
references.citation: J Affect Disord. 2012 May;138(3):468-72
references.pmid: 22357335
references.citation: Science. 2007 Apr 20;316(5823):445-9
references.pmid: 17363630
references.citation: J Am Acad Child Adolesc Psychiatry. 2006 Jun;45(6):691-699
references.pmid: 16721319
references.citation: Front Neuroendocrinol. 2009 Oct;30(4):534-547
references.pmid: 19481567