title: A Pooled Genome-Wide Association Study of Asperger Syndrome.
abstract: Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Varun
authors.initials: V
authors.lastname: Warrier
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading, United Kingdom.
authors.forename: Bhismadev
authors.initials: B
authors.lastname: Chakrabarti
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Allen
authors.initials: A
authors.lastname: Chan
authors.affiliation: MRC Centre for Social, Genetic and Developmental Psychiatry, King's College London, Institute of Psychiatry, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Craig
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Uma
authors.initials: U
authors.lastname: Mallya
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lakatošová
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Karola
authors.initials: K
authors.lastname: Rehnstrom
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Wheelwright
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Carrie
authors.initials: C
authors.lastname: Allison
authors.affiliation: Max Planck Institute for Psycholinguistics, 6500 AH, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
mesh_terms: D020817:Asperger Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide