Table10_Integration of multiple-omics data to reveal the shared genetic architecture of educational attainment, intelligence, cognitive performance, and Alzheimer’s disease.XLSX

Growing evidence suggests the effect of educational attainment (EA) on Alzheimer’s disease (AD), but less is known about the shared genetic architecture between them. Here, leveraging genome-wide association studies (GWAS) for AD (N = 21,982/41,944), EA (N = 1,131,881), cognitive performance (N = 257,828), and intelligence (N = 78,308), we investigated their causal association with the linkage disequilibrium score (LDSC) and Mendelian randomization and their shared loci with the conjunctional false discovery rate (conjFDR), transcriptome-wide association studies (TWAS), and colocalization. We observed significant genetic correlations of EA (rg = −0.22, p = 5.07E-05), cognitive performance (rg = −0.27, p = 2.44E-05), and intelligence (rg = −0.30, p = 3.00E-04) with AD, and a causal relationship between EA and AD (OR = 0.74, 95% CI: 0.58–0.94, p = 0.013). We identified 13 shared loci at conjFDR <0.01, of which five were novel, and prioritized three causal genes. These findings inform early prevention strategies for AD.

越来越多的研究证据表明，教育程度（Educational Attainment，EA）对阿尔茨海默病（Alzheimer’s disease，AD）存在影响，但上述教育程度、认知表现、智力与阿尔茨海默病间的共享遗传结构仍有待系统阐明。本研究依托针对阿尔茨海默病（样本量N=21982/41944）、教育程度（N=1131881）、认知表现（N=257828）及智力（N=78308）的全基因组关联研究（Genome-Wide Association Studies，GWAS）数据集，采用连锁不平衡评分（Linkage Disequilibrium Score，LDSC）与孟德尔随机化（Mendelian randomization）方法，探究上述四类表型与阿尔茨海默病的因果关联，并通过联合错误发现率（conjunctional false discovery rate，conjFDR）、转录组全关联研究（Transcriptome-Wide Association Studies，TWAS）及共定位分析，鉴定它们之间的共享遗传位点。研究结果显示，教育程度（rg=-0.22，p=5.07×10^-5）、认知表现（rg=-0.27，p=2.44×10^-5）与智力（rg=-0.30，p=3.00×10^-4）均与阿尔茨海默病存在显著遗传相关；同时证实教育程度与阿尔茨海默病间存在因果关系（优势比OR=0.74，95%置信区间CI：0.58–0.94，p=0.013）。本研究在conjFDR<0.01的阈值下共鉴定出13个共享遗传位点，其中5个为全新未报道的位点，并优先筛选出3个因果基因。上述发现可为阿尔茨海默病的早期预防策略提供科学依据。