A genome‐wide association meta‐analysis of all‐cause and vascular dementia

Figures

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  FIGURE 1. Manhattan plot of ACD GWAS. In addition to variants in APOE region, we identified five new genetic loci associated with VaD. Blue and red lines correspond to p value of 5e−7 and 5e−8 for genome‐wide suggestive and significant SNPs, respectively. Manhattan plots for the cross‐ancestry meta‐analysis. Each dot represents a SNP, the x‐axis shows the chromosomes where each SNP is located, and the y‐axis shows −log10 p value of the association of each SNP with ACD in the cross‐ancestry meta‐analysis. The red horizontal line shows the genome‐wide significant threshold (p value = 5e‐8; −log10 p value = 7.30). The nearest gene to the most significant SNP in each locus has been labeled.

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  FIGURE 2. Manhattan plot of VaD GWAS. In addition to variants in the APOE region, we identified five new genetic loci associated with VaD. Blue and red lines correspond to a p value of 5e−7 and 5e−8 for genome‐wide suggestive and significant SNPs, respectively. Manhattan plots for cross‐ancestry meta‐analysis. Each dot represents a SNP, the x‐axis shows the chromosomes where each SNP is located, and the y‐axis shows the −log10 p value of the association of each SNP with VaD in the cross‐ancestry meta‐analysis. The red horizontal line shows the genome‐wide significant threshold (p value = 5e‐8; −log10 p value = 7.30). The gene closest to the most significant SNP in each locus has been labeled.

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  FIGURE 3. Q‐Q plots of ACD (left) and VaD (right) GWASs. The expected p values (x‐axis) are plotted against the observed p values (y‐axis). The units of the axes are the −log10 of the p value. The red and blue curves represent the plots with MAF ≥ 0.05 and 0.01, respectively. The diagonal line of the null hypothesis and its 95% confidence interval are plotted in gray based on the p values without the previously reported SNPs. The red dotted line represents the cutoff for genome‐wide significance. MAF, minor allele frequency.

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  FIGURE 4. Shared genetic contribution between ACD/VaD and related risk factors. Contributions determined by LD score regression analysis (LDSR) (top), and Genetic Covariation Analyzer (GNOVA) (bottom). Effect sizes (rg) and significance levels (logp) are represented by color and symbol size. AD, Alzheimer's disease; GCF, general cognitive function; all stroke (AS) and its subtypes (ischemic, IS; cardioembolic, CES; small vessel, SVS; large artery, LAS); WMH, white matter hyperintensity burden; DBP, diastolic blood pressure; SBP, systolic blood pressure; PP, pulse pressure; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein. Diamond shape: non‐significant. Cross‐significant causal effect estimates from MR‐LAP analysis.