A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults

1] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn, Germany.
Translational Psychiatry (Impact Factor: 5.62). 02/2013; 3(2):e229. DOI: 10.1038/tp.2012.148
Source: PubMed


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.

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Available from: Philipp G Sämann, Mar 15, 2014
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    • "We used two maths scores; (1) the arithmetic subtest of the Wechsler Intelligence Scale for Children (WISC) (Wechsler 1992), which consists of verbal maths problems that require basic calculation skills and (2) a maths achievement factor score (MA; Nunes et al. 2012), derived from UK national curriculum maths tests taken between 10 and 14 years of age (Table 1). The variables were selected because they predominantly focused on basic computational skills, similar to those used in the TEDS study (Ludwig et al. 2013). Data on these measures approximate a normal distribution. "
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    ABSTRACT: Twin studies indicate that dyscalculia (or mathematical disability) is caused partly by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities and the only one reaching genome-wide statistical significance. We conducted a replication study in different cohorts to assess the effect of rs133885 maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC), (N = 3819). We tested additional cohorts including the York Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine Cohort, and stratified them for a definition of dyslexia whenever possible. We did not observe any associations between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results suggest that the myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities. This article is protected by copyright. All rights reserved.
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    • "The gene characterized by the highest number of differentiated nonsynonymous SNPs was MYO18B, encoding unconventional myosin XVIIIb. Previous studies have demonstrated the important role of this gene in myocardic structures (Ajima et al. 2008), as well as its contribution to cognitive phenotypes (Purcell et al. 2009; Ludwig et al. 2013). Another interesting gene is insulin-like growth factor 2 (IGF2) its expression increases in response to endurance training and extent of this change differs between humans with highest and lowest improvement in aerobic capacity (Keller et al. 2011). "
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