title: The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure.
abstract: Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scerri
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Darki
authors.forename: Dianne F
authors.initials: DF
authors.lastname: Newbury
authors.forename: Andrew J O
authors.initials: AJ
authors.lastname: Whitehouse
authors.forename: Myriam
authors.initials: M
authors.lastname: Peyrard-Janvid
authors.forename: Hans
authors.initials: H
authors.lastname: Matsson
authors.forename: Qi W
authors.initials: QW
authors.lastname: Ang
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: Susan
authors.initials: S
authors.lastname: Ring
authors.forename: John
authors.initials: J
authors.lastname: Stein
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Joel B
authors.initials: JB
authors.lastname: Talcott
authors.forename: Torkel
authors.initials: T
authors.lastname: Klingberg
authors.forename: Silvia
authors.initials: S
authors.lastname: Paracchini
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D002648:Child; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000648:ultrastructure*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D003952:Diagnostic Imaging / Q000379:methods; D004410:Dyslexia / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007361:Intelligence Tests; D007802:Language; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism; D016366:Open Reading Frames; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors