Genome-wide quantitative trait locus association scan of general cognitive ability using pooled DNA and 500K single nucleotide polymorphism microarrays.
Genome-wide quantitative trait locus association scan of general cognitive ability using pooled DNA and 500K single nucleotide polymorphism microarrays.
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DOI：
10.1111/j.1601-183x.2007.00368.x
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发表时间：
2008-06
影响因子：
2.5
通讯作者：
Plomin, R.
中科院分区：
文献类型：
--
作者：
Butcher, L. M.;Davis, O. S. P.;Craig, I. W.;Plomin, R.
一般认知能力（g）是指认知能力的共同点，是分子遗传学研究的重要目标，因为多变量定量遗传分析表明，同一组基因会影响不同的认知能力以及学习障碍。在 g 的首次常染色体全基因组关联扫描中，我们使用两阶段数量性状基因座 (QTL) 设计和混合 DNA，从 7000 名 7 岁儿童样本中筛选出微阵列上超过 500 000 个单核苷酸多态性 (SNP)。在第一阶段，我们筛选了低 g 和高 g 汇集组之间的等位基因频率差异。在第二阶段，通过对 3195 名独立样本进行单独基因分型，对第一阶段提名的 47 个 SNP 进行了测试，这些样本代表了 7000 名 7 岁儿童的 g 分数的整个分布。六个 SNP 在 g 的正态分布中产生了显着关联，尽管在施加 0.05 的错误发现率后，只有一个 SNP 仍然显着。然而，这些 SNP 中没有一个占 g 方差超过 0.4%，尽管检测该大小关联的功效为 95%。即使对于认知能力和残疾等高度遗传的性状，QTL 效应大小也可能比之前假设的要小得多。尽管如此，六个 SNP 的聚合“SNP 集”与 g 的相关性为 0.11 (P < 0.00000003)。这表明未来的 SNP 集将包含更多的 SNP，可用于预测遗传风险和研究从基因到大脑到行为的影响功能系统。
General cognitive ability (g), which refers to what cognitive abilities have in common, is an important target for molecular genetic research because multivariate quantitative genetic analyses have shown that the same set of genes affects diverse cognitive abilities as well as learning disabilities. In this first autosomal genome-wide association scan of g, we used a two-stage quantitative trait locus (QTL) design with pooled DNA to screen more than 500 000 single nucleotide polymorphisms (SNPs) on microarrays, selecting from a sample of 7000 7-year-old children. In stage 1, we screened for allele frequency differences between groups pooled for low and high g. In stage 2, 47 SNPs nominated in stage 1 were tested by individually genotyping an independent sample of 3195 individuals, representative of the entire distribution of g scores in the full 7000 7-year-old children. Six SNPs yielded significant associations across the normal distribution of g, although only one SNP remained significant after a false discovery rate of 0.05 was imposed. However, none of these SNPs accounted for more than 0.4% of the variance of g, despite 95% power to detect associations of that size. It is likely that QTL effect sizes, even for highly heritable traits such as cognitive abilities and disabilities, are much smaller than previously assumed. Nonetheless, an aggregated ‘SNP set’ of the six SNPs correlated 0.11 (P < 0.00000003) with g. This shows that future SNP sets that will incorporate many more SNPs could be useful for predicting genetic risk and for investigating functional systems of effects from genes to brain to behavior.