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=Volume 14 - 2023

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=Growing evidence suggests the effect of educational attainment (EA) on Alzheimer's disease (AD), but less is known about the shared genetic architecture of 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 linkage disequilibrium score (LDSC) and Mendelian randomization and their shared loci with 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 5 were novel, and prioritized 3 causal genes. These findings inform early prevention strategies for AD.