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

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.

Predicting the causal relationship between polyunsaturated fatty acids and cerebral aneurysm risk from a Mendelian randomization study

“…Third, we clustered SNPs in linkage disequilibrium (LD, R2≥0.001 and within 10 mb). Fourth, to eliminate unclear, palindromic and associated with known confounding factors (body mass index (McDowell et al, 2018), blood pressure (Sun et al, 2022), type 2 diabetes (Tian et al, 2022), high-density lipoprotein (Huang et al, 2018)) SNPs. Fifth, If an instrumental SNP for the exposure was not available from the outcome data set, we replaced it with a suitable proxy SNP (r 2 >0.8 in the European 1000 Genomes Project reference panel using LDlink https://ldlink.nci.nih.gov/]) or removed it in the absence of such a proxy.…”

Predicting the causal relationship between polyunsaturated fatty acids and cerebral aneurysm risk from a Mendelian randomization study

“…Third, we clustered SNPs in linkage disequilibrium (LD, R2≥0.001 and within 10 mb). Fourth, to eliminate unclear, palindromic and associated with known confounding factors (body mass index (McDowell et al, 2018 ), blood pressure (Sun et al, 2022 ), type 2 diabetes (Tian et al, 2022 ), highdensity lipoprotein (Huang et al, 2018 )) SNPs. Fifth, If an instrumental SNP for the exposure was not available from the outcome data set, we replaced it with a suitable proxy SNP (r 2 >0.8 in the European 1000 Genomes Project reference panel using LDlink https://ldlink.nci.nih.gov/ ]) or removed it in the absence of such a proxy.…”

Potential application of peripheral blood biomarkers in intracranial aneurysms

“…The role of peripheral blood lipids in IAs is a highly studied area. Tian et al ( 33 ) performed a Mendelian randomization study and found a significant causal relationship between obesity and IAs. There was a positive correlation between the fat percentage in the body and the risk of IA rupture.…”