Frontiers in Genetics (Oct 2023)

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

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

DOI
https://doi.org/10.3389/fgene.2023.1243879
Journal volume & issue
Vol. 14

Abstract

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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.

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