A two-sample Mendelian randomization analysis of modifiable risk factors and intracranial aneurysms - PubMed (original) (raw)

A two-sample Mendelian randomization analysis of modifiable risk factors and intracranial aneurysms

Danyang Tian et al. Sci Rep. 2022.

Abstract

We aimed to investigate the causality between potentially modifiable risk factors and the risk of intracranial aneurysm. Genetic instruments for 51 modifiable factors and intracranial aneurysm data were obtained from recently published genome-wide association studies. We applied two-sample Mendelian randomization methods to investigate their causal relationships. Genetically predicted cigarettes per day, smoking initiation, systolic blood pressure, hypertension and body fat percentage were significantly associated with an increased risk of intracranial aneurysm [odds ratios (OR) 2.67, 95% confidence interval (CI) 1.75-4.07, p = 5.36 × 10-6, OR 1.53, 95% CI 1.32-1.77, p = 9.58 × 10-9, OR 1.05, 95% CI 1.02-1.08, p = 1.18 × 10-3, OR 1.65, 95% CI 1.19-2.28, p = 2.56 × 10-3 and OR 1.29, 95% CI 1.11-1.52, p = 1.33 × 10-3, respectively]. Type 2 diabetes mellitus was significantly associated with a decreased risk of intracranial aneurysm (OR 0.89, 95% CI 0.83-0.95, p = 8.54 × 10-4). Body fat percentage was significantly associated with subarachnoid haemorrhage (p = 5.70 × 10-5). This study provided genetic evidence of causal effects of smoking, blood pressure, type 2 diabetes mellitus and obesity on the risk of intracranial aneurysm.

© 2022. The Author(s).

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Figure 1

Schematic representation of Mendelian randomization analysis. Broken lines represent potential pleiotropic or direct causal effects between variables that would violate Mendelian randomization assumptions.

Figure 2

Figure 2

Mendelian randomization for associations between traits of lifestyle and cardio-metabolic risk factors and intracranial aneurysm. SNP: single nucleotide polymorphism; OR: odds ratios; CI: confidence interval; BMI: body mass index; MVPA: moderate-to-vigorous physical activity; SBP: systolic blood pressure; DBP: diastolic blood pressure; PP: pulse pressure; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TC: total cholesterol; TG: triglyceride; T2DM: type 2 diabetes mellitus; HbA1c: hemoglobin A1c; WHR: waist hip ratio.

Figure 3

Figure 3

Mendelian randomization for associations between traits of cardio-metabolic, nutrients and dietary intake, impaired renal function and inflammation risk factors and intracranial aneurysm. SNP: single nucleotide polymorphism; OR: odds ratios; CI: confidence interval; BMI: body mass index; CIMT: carotid intima media thickness; CRP: C reactive protein; eGFR: estimated glomerular filtration rate; SLE: systemic lupus erythematosus; TMAO: trimethylamine-n-oxide.

Figure 4

Figure 4

Mendelian randomization for associations between significant risk factors and intracranial aneurysm, subarachnoid haemorrhage and unruptured intracranial aneurysm. SNP: single nucleotide polymorphism; OR: odds ratios; CI: confidence interval; IA: intracranial aneurysm; SAH: subarachnoid haemorrhage; UIA: unruptured intracranial aneurysm; TRANS: trans-ethnics.

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