Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151).
Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151).
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DOI：
10.1038/mp.2016.45
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发表时间：
2016-06
影响因子：
11
通讯作者：
Deary IJ
中科院分区：
文献类型：
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作者：
Davies G;Marioni RE;Liewald DC;Hill WD;Hagenaars SP;Harris SE;Ritchie SJ;Luciano M;Fawns-Ritchie C;Lyall D;Cullen B;Cox SR;Hayward C;Porteous DJ;Evans J;McIntosh AM;Gallacher J;Craddock N;Pell JP;Smith DJ;Gale CR;Deary IJ
人们在认知功能上的差异部分是遗传的，并且与重要的生活结果有关。先前的认知功能全基因组关联（GWA）研究已经发现了多基因效应的证据，但迄今为止，很少有重复的遗传关联。在这里，我们使用来自英国生物银行样本的数据来调查基因对三种认知功能和教育程度测试差异的贡献。GWA对言语-数值推理（N=36 035）、记忆（N=112 067）、反应时间（N=111 483）和获得大专或大学学位（N=111 114）进行了分析。我们报告了在20个基因组区域中基于单核苷酸多态性（SNP）的全基因组显著关联，以及在46个区域中基于基因的显著发现。这些发现包括ATXN2、CYP2DG、APBA1和CADM2基因。我们在已发表的GWA关于认知功能、受教育程度和儿童智力的研究中报告了这些结果的重复。在UK Biobank中，也有先前在GWA关于受教育程度和认知功能的研究中报道的SNP的重复。GCTA-GREML分析，使用共同snp（小等位基因频率>.01），表明基于snp的显著遗传率在语言-数值推理方面为31% (s.e.m.=1.8%)，在记忆方面为5% (s.e.m.=0.6%)，在反应时间方面为11% (s.e.m.=0.6%)，在教育程度方面为21% （s.e.m.=0.6%）。多基因评分分析表明，在一个独立的队列中，高达5%的认知测试分数差异是可以预测的。确定的基因组区域包括几个新的基因座，其中一些与颅内容量、神经变性、阿尔茨海默病和精神分裂症有关。
People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.