Study design

Basic information of 16 outcome traits in MRC IEU OpenGWAS

Categories of the exposure traits identified by IVW model

80 exposure traits with causal effects on the main outcome traits of AD based on major analysis method random-effects IVW model.

Figure 4A. Thirty-two blood lipids and lipoproteins items that were positively associated with the main outcome traits of AD. Figure 4B. Four blood lipids and lipoproteins items that were negatively associated with the main outcome traits of AD. Figure 4C. Twelve immunological test items that were positively associated with the main outcome traits of AD. Figure 4D. Three plasma protein tests items that were negatively associated with the main outcome traits of AD. Figure 4E. Ten family history items with causal effects on the main outcome traits of AD. Figure 4F. Nine diseases items with causal effects on the main outcome traits of AD. Figure 4G. Seven molecular trait items with causal effects on the main outcome traits of AD. Figure 4H. Three lifestyle trait items with causal effects on the main outcome traits of AD.

Note: The pink dots in the figure represent positive association, the blue dots in the figure represent negative association, with the color depth of the dots being positively proportional to the OR value (the darker the color, the larger the OR value), and the size of the dots being inversely proportional to the p-value (the smaller the p-value, the larger the dots). The gray dots represent no significant causal association (p>0.05).

Statistical models for causal effect results of seven molecular trait items with causal effects on the main outcome traits of AD.

Note:

(i) For column Inverse variance weighted, MR egger, Weighted median, Simple mode, Weighted mode, Maximum likelihood, and Penalized weighted median: the pink dots in the figure represent positive association, the blue dots represent negative association, with the color depth of the dots being positively proportional to the OR value (the darker the color, the larger the OR value), and the size of the dots being inversely proportional to the p-value (the smaller the p-value, the larger the dots). The gray dots represent no significant causal association (p>0.05). The star mark(✪) represents that is significant at the Bonferroni threshold (p<1.727e-07).

(ii) For column Heterogeneity test: the pink dots in the figure represent the effect of heterogeneity was considered negligible (heterogeneity_pval> 0.05).

The gray dots represent significant association (p<0.05).

(iii) For column Egger intercept test: the pink dots in the figure represent there was no significant difference between Egger Intercept and 0, indicating no horizontal pleiotropy (Horizontal_pval> 0.05). The gray dots represent significant association (p<0.05). The dark gray dots represent not applicable due to the quantity of SNP was less than 3.