WSO - March 2023 - 349

Du et al.
349
Figure 2. Odds ratio for the association among genetically predicted ADHD and AIS, LAS, CES, and SVS.
OR: odds ratio; 95% CI: 95% confidence interval; ADHD: attention-deficit/hyperactivity disorder; AIS: any ischemic stroke; LAS: large-artery
atherosclerotic stroke; CES: cardioembolic stroke; SVS: small-vessel stroke.
Estimates are per one-unit increase in ADHD. Intercept is expressed as beta ± standard error.
(OR = 1.20 per one-unit increase in loge odds of ADHD,
95% CI = 1.02-1.41, P = 0.030). There was little evidence
of a causal effect of ADHD on SVS. The effect sizes of
SNPs on ADHD versus ischemic stroke and its subtypes
were shown in Figure 3.
For all four outcomes, the causal estimates from the
median-based (simple and weighted), MR-RAPS, and
MR-PRESSO were consistent with that from IVW, although
the CIs were wider as expected (Figure 2 and Supplementary
Table 4). The MR-Egger analysis suggests that ADHD has a
causal effect on LAS but not AIS, CES, or SVS. No directional
pleiotropy was detected by either the MR-Egger intercept
test or the MR-PRESSO global test, and the Cochran Q
test did not identify significant heterogeneity among SNPs
used as instrumental variables (Supplementary Table 5).
Leave-one-out analyses did not identify any individual SNP
that dominated overall estimates (Supplementary Figure 1).
Checking for mediators between ADHD and
ischemic stroke subtypes
In the MVMR modeling where genetic variants for
ADHD and CAD were simultaneously entered, the
causal estimate of ADHD on LAS was attenuated to 1.34
(95% CI = 0.95-1.89, P = 0.100), compared to 1.40 (95%
CI = 1.10-1.76, P = 0.005) in univariable MR; the causal
International Journal of Stroke, 18(3)

WSO - March 2023

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