AUTHOR=Wang Fuxu , Wang Haoyan , Yuan Ye , Han Bing , Qiu Shizheng , Hu Yang , Zang Tianyi 

TITLE=Integration of multiple-omics data to reveal the shared genetic architecture of educational attainment, intelligence, cognitive performance, and Alzheimer’s disease

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1243879

DOI=10.3389/fgene.2023.1243879

ISSN=1664-8021

ABSTRACT=<p>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 (r<sub>g</sub> = −0.22, <italic>p</italic> = 5.07E-05), cognitive performance (r<sub>g</sub> = −0.27, <italic>p</italic> = 2.44E-05), and intelligence (r<sub>g</sub> = −0.30, <italic>p</italic> = 3.00E-04) with AD, and a causal relationship between EA and AD (OR = 0.74, 95% CI: 0.58–0.94, <italic>p</italic> = 0.013). We identified 13 shared loci at conjFDR &lt;0.01, of which five were novel, and prioritized three causal genes. These findings inform early prevention strategies for AD.</p>