Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, United Kingdom; CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Cambridgeshire, United Kingdom.
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, United Kingdom.
PLoS One. 2014 May 6;9(5):e96374. doi: 10.1371/journal.pone.0096374. eCollection 2014.
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.
数学能力是可遗传的，但很少有研究直接探讨其分子遗传基础。在这里，我们旨在确定特定的遗传因素对数学能力变化的贡献。我们使用基于英国样本中学期末学术考试成绩的两组 pooled DNA 进行了全基因组关联扫描：高（n=419）与低（n=183）数学能力，同时控制了他们的语言能力。在使用 Affymetrix GeneChip Human Mapping 版本 6.0 阵列的 906600 个 SNPs 中，搜索了这些组之间等位基因频率的显著差异。在 pooled 关联分析中达到 p<1.5×10(-5)的阈值后，从 12 个 SNPs 中选择 12 个 SNPs 进行了 542 名参与者的个体基因分型，并对其进行了分析以验证初始关联（最低 p 值为 1.14×10(-6)）。在这项分析中，一个 SNP（rs789859）在 Bonferroni 校正后显示出显著的关联，而四个 SNP（rs10873824、rs4144887、rs12130910 和 rs2809115）则具有名义上的显著性（最低 p 值为 3.278×10(-4)）。三个感兴趣的 SNP 位于已知基因（FAM43A、SFT2D1 和 C14orf64）内或附近。显示最强关联的 SNP rs789859 位于先前与学习困难和自闭症相关的染色体 3q29 区域。rs789859 位于 LSG1 的下游 1.3 kbp 处，FAM43A 的上游 700 bp 处，映射到后者的潜在启动子/调控区域内。据我们所知，这是第二项研究遗传变异与数学能力之间关联的研究，它突出了一些有趣的标记，以供未来研究。
