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

Abstract

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.

Evidence for the gut‐skin axis: Common genetic structures in inflammatory bowel disease and psoriasis

“…This is because their genetic risk architecture is generally based on common genetic variants with small effect sizes 19 . Fortunately, some novel genetic statisticians can solve this challenge by estimating the correlation of genetic structure between two complex diseases at multiple levels using GWAS summary statistics 20‐23 . These methods were employed to enhance the understanding of the shared genetic structure and causal relationships between Ps and IBD.…”