Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Institute of Mental Health, Singapore, 539747, Singapore.
Nat Commun. 2018 May 29;9(1):2098. doi: 10.1038/s41467-018-04362-x.
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
一般认知功能是一种突出且相对稳定的人类特征，与许多重要的生活结果相关。我们结合了 CHARGE 和 COGENT 联盟以及英国生物库的认知和遗传数据（总计 N=300486；年龄 16-102），发现了 148 个与一般认知功能相关的全基因组显著独立位点（P<5×10）。在新的遗传位点内，有与神经退行性和神经发育障碍、身体和精神疾病以及大脑结构相关的变异。基于基因的分析发现了 709 个与一般认知功能相关的基因。大脑皮层的表达水平与一般认知功能相关。使用多基因评分，可在独立样本中预测高达 4.3%的一般认知功能的方差。我们检测到一般认知功能、反应时间和许多健康变量（包括视力、高血压和长寿）之间存在显著的遗传重叠。总之，我们确定了新的遗传位点和途径，有助于一般认知功能的遗传性。
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