title: A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.
abstract: Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10(-5), 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10(-6)). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 × 10(-4)). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, United Kingdom; CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Cambridgeshire, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, 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: 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, Cambridgeshire, United Kingdom.
authors.forename: Uma
authors.initials: U
authors.lastname: Mallya
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, 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, Cambridgeshire, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Wheelwright
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, 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, Cambridgeshire, United Kingdom.
authors.forename: Varun
authors.initials: V
authors.lastname: Warrier
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics*; D008297:Male; D008433:Mathematics / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*