title: A common variant in myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults.
abstract: The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities (P(comb) = 7.71 × 10(-10), n = 699), with an effect size of 4.87%. This association was also found in a sample from the general population (P = 0.048, n = 1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.
authors: Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors: K U
authors: KU
authors: Ludwig
authors: P
authors: P
authors: Sämann
authors: M
authors: M
authors: Alexander
authors: J
authors: J
authors: Becker
authors: J
authors: J
authors: Bruder
authors: K
authors: K
authors: Moll
authors: D
authors: D
authors: Spieler
authors: M
authors: M
authors: Czisch
authors: A
authors: A
authors: Warnke
authors: S J
authors: SJ
authors: Docherty
authors: O S P
authors: OS
authors: Davis
authors: R
authors: R
authors: Plomin
authors: M M
authors: MM
authors: Nöthen
authors: K
authors: K
authors: Landerl
authors: B
authors: B
authors: Müller-Myhsok
authors: P
authors: P
authors: Hoffmann
authors: J
authors: J
authors: Schumacher
authors: G
authors: G
authors: Schulte-Körne
authors: D
authors: D
authors: Czamara
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics; D002648:Child; D060705:Dyscalculia / Q000235:genetics* / Q000503:physiopathology; D004410:Dyslexia / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D008297:Male; D009218:Myosins / Q000235:genetics*; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000033:anatomy & histology* / Q000503:physiopathology; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C500982:MYO18B protein, human; D025521:Tumor Suppressor Proteins; D009218:Myosins