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. 2024 Feb 14:15:1346703.
doi: 10.3389/fneur.2024.1346703. eCollection 2024.

Causal association between depression and intracranial aneurysms: a bidirectional two-sample Mendelian randomization study

Jujiang Wu #  1 , Hao Sun #  1 , Junqiang Ma  1   2
Affiliations

Causal association between depression and intracranial aneurysms: a bidirectional two-sample Mendelian randomization study

Jujiang Wu et al. Front Neurol. .

Abstract

Background: Although observational studies have suggested a bidirectional relation between depression and intracranial aneurysms (IAs), their causal relations remain unclear. Thus we aimed to assess the causal association between depression and IAs.

Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study using summary-level data from publicly available genome-wide association studies of depression (n = 500,199), IAs (n = 79,429), unruptured intracranial aneurysm (uIA) (n = 74,004), and subarachnoid hemorrhage (SAH) (n = 77,074). MR analyses included the inverse-variance weighted (IVW) method as the primary analytic, plus weighted-median, simple mode, weighted mode, MR-Egger, and MR PRESSO.

Results: Genetically predicted depression was strongly positively related to IAs (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.19-2.39, p = 0.003), uIA (OR = 1.96, 95% CI 1.06-3.64, p = 0.032), and SAH (OR = 1.73, 95% CI 1.14-2.61, p = 0.009). Reverse MR analyses showed that while genetically predicted uIA was positively related to depression (OR = 1.02, 95% CI 1.00-1.05, p = 0.044), no causal relations were observed for either IAs or SAH for depression.

Conclusion: Our findings provide evidence of a causal effect of depression on IAs, uIA, and SAH. For the reverse MR analyses, we found a causal impact of uIA on depression, but no causal influence of either IAs or SAH for depression.

Keywords: Mendelian randomization; causal association; depression; intracranial aneurysms; subarachnoid hemorrhage.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of bidirectional MR study design. SNPs, single nucleotide polymorphisms; IVs, instrumental variables; IAs, intracranial aneurysms; uIA, unruptured intracranial aneurysm; SAH, subarachnoid hemorrhage; MR, Mendelian randomization. MR analysis depends on three major assumptions: Assumption 1, IVs are strongly associated with exposure; Assumption 2, IVs are independent of confounders; Assumption 3, IVs are not directly related to outcomes.
Figure 2
Figure 2
Forest plots of causal effects of depression on IAs, uIA, and SAH. IAs, intracranial aneurysms; uIA, unruptured intracranial aneurysm; SAH, subarachnoid hemorrhage; IVs, instrumental variables; IVW, inverse-variance weighted; MR, Mendelian randomization; OR, odds ratio; 95% CI, 95% confidence interval.
Figure 3
Figure 3
Forest plots of causal effects of IAs, uIA, and SAH on depression. IAs, intracranial aneurysms; uIA, unruptured intracranial aneurysm; SAH, subarachnoid hemorrhage; IVs, instrumental variables; IVW, inverse-variance weighted; MR, Mendelian randomization; OR, odds ratio; 95% CI, 95% confidence interval.
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