Peng Qian, Schork Nicholas J, Wilhelmsen Kirk C, Ehlers Cindy L
Department of Neuroscience, The Scripps Research Institute, La Jolla, California.
Department of Human Biology, J. Craig Venter Institute, La Jolla, California.
Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):435-450. doi: 10.1002/ajmg.b.32533. Epub 2017 Apr 24.
EEG alpha activity is the dominant oscillation in most adult humans, is highly heritable, and has been associated with a number of cognitive functions. Two EEG phenotypes, low- and high-voltage alpha (LVA & HVA), have been demonstrated to have high heritabilities. They have different prevalence depending on a population's ancestral origins. In the present study we assessed the influence of ancestry admixture on EEG alpha power, and conducted a whole genome sequencing association analysis and an ancestry-informed polygenic study on those phenotypes in a Native American (NA) population that has a high prevalence of LVA. Seven common variants, in LD with each other upstream from gene ASIC2, reached genome-wide significance (p = 2 × 10 ) having a positive association with alpha voltage. They had lower minor allele frequencies in the NAs than in a global population sample. Overall correlations between lower degrees of NA (higher degree European) ancestry and HVA, and higher degrees of NA and LVA were also found. Additionally a rare-variant gene-based study identified gene TIA1 being negatively associated with LVA. Approximately 3% of SNPs exhibited a 15-fold enrichment that explained nearly half of the total SNP-heritability for EEG alpha. These regions showed the most significant anti-correlations between NA ancestry and alpha voltage, and were enriched for genes and pathways mediating cognitive functions. Our findings suggested that these regions likely harbor causal variants for HVA, and lacking of such variants could explain the high prevalence of LVA in this NA population, possibly illuminating the ancestral origin and genetic basis for EEG alpha.
脑电图阿尔法活动是大多数成年人的主要振荡，具有高度遗传性，并与多种认知功能相关。两种脑电图表型，即低电压和高电压阿尔法（LVA和HVA），已被证明具有高遗传性。它们的患病率因人群的祖先来源而异。在本研究中，我们评估了祖先混合对脑电图阿尔法功率的影响，并对一个LVA患病率高的美洲原住民（NA）人群中的这些表型进行了全基因组测序关联分析和祖先知情多基因研究。在基因ASIC2上游彼此处于连锁不平衡状态的七个常见变异达到全基因组显著性（p = 2×10），与阿尔法电压呈正相关。它们在美洲原住民中的次要等位基因频率低于全球人群样本。还发现了较低程度的NA（较高程度的欧洲）祖先与HVA之间以及较高程度的NA与LVA之间的总体相关性。此外，一项基于罕见变异基因的研究确定基因TIA1与LVA呈负相关。大约3%的单核苷酸多态性（SNP）表现出15倍的富集，解释了脑电图阿尔法总SNP遗传性的近一半。这些区域显示出NA祖先与阿尔法电压之间最显著的反相关性，并且富含介导认知功能的基因和途径。我们的研究结果表明，这些区域可能含有HVA的因果变异，而缺乏这些变异可以解释该NA人群中LVA的高患病率，这可能为脑电图阿尔法的祖先起源和遗传基础提供线索。
