A genome-wide association study identifies multiple loci associated with mathematics ability and disability
A genome-wide association study identifies multiple loci associated with mathematics ability and disability
复制标题
DOI：
10.1111/j.1601-183x.2009.00553.x
复制
发表时间：
2010-03-01
影响因子：
2.5
通讯作者：
Plomin, R.
中科院分区：
文献类型：
--
作者：
Docherty, S. J.;Davis, O. S. P.;Plomin, R.
计算能力与识字能力同样重要，并且表现出相似的残疾频率。尽管其病因尚不清楚，但定量遗传学研究已证明数学能力具有适度的遗传性。在第一个关于数学能力和残疾的全基因组关联研究 (GWAS) 中，从两个高能力与低能力（每个 600 名 10 岁儿童）的混合 DNA 扫描提名的 43 个单核苷酸多态性 (SNP) 关联中，有 10 个在涵盖整个数学能力分布的 *2356 个人的单独基因分型样本中得到了验证 (P < 0.05)，并通过教师报告和在线测试进行了评估。尽管目前对于复杂性状的预期影响不大，并且需要进一步复制，但其中涉及一些有趣的候选基因，例如编码神经元细胞粘附分子的 NRCAM。当组合成一组时，10 个 SNP 占表型方差的 2.9% (F = 56.85; df = 1 和 1881; P = 7.277e-14)。该关联在整个分布中呈线性关系，与数量性状基因座 (QTL) 假设一致；在我们的样本中，拥有 20 个风险等位基因中的 10 个或更多的儿童中，有三分之一的儿童处于表现最低的 15% 分布中的可能性几乎是其两倍（OR = 1.96；df = 1；P = 3.696e-07）。我们的结果与定量遗传学研究的结果一致，表明数学能力和残疾受到许多基因的影响，这些基因在整个能力范围内产生微小的影响，这意味着需要更高效的研究来检测和复制这些 QTL 关联。
Numeracy is as important as literacy and exhibits a similar frequency of disability. Although its etiology is relatively poorly understood, quantitative genetic research has demonstrated mathematical ability to be moderately heritable. In this first genome-wide association study (GWAS) of mathematical ability and disability, 10 out of 43 single nucleotide polymorphism (SNP) associations nominated from two high- vs. low-ability (n = 600 10-year-olds each) scans of pooled DNA were validated (P < 0.05) in an individually genotyped sample of *2356 individuals spanning the entire distribution of mathematical ability, as assessed by teacher reports and online tests. Although the effects are of the modest sizes now expected for complex traits and require further replication, interesting candidate genes are implicated such as NRCAM which encodes a neuronal cell adhesion molecule. When combined into a set, the 10 SNPs account for 2.9% (F = 56.85; df = 1 and 1881; P = 7.277e-14) of the phenotypic variance. The association is linear across the distribution consistent with a quantitative trait locus (QTL) hypothesis; the third of children in our sample who harbour 10 or more of the 20 risk alleles identified are nearly twice as likely (OR = 1.96; df = 1; P = 3.696e-07) to be in the lowest performing 15% of the distribution. Our results correspond with those of quantitative genetic research in indicating that mathematical ability and disability are influenced by many genes generating small effects across the entire spectrum of ability, implying that more highly powered studies will be needed to detect and replicate these QTL associations.