The affiliation between smoking and subarachnoid hemorrhage

Genetically determined smoking behavior is associated with an increased risk of non-traumatic subarachnoid hemorrhage (SAH), according to study results published in Stroke.

The data suggest that smoking is a major risk factor for aneurysm formation and rupture. While previous studies have identified an increased risk of non-traumatic SAH in smokers, the causal relationship is not well understood. The aim of this study was to determine whether smoking is causally related to the risk of SAH.

Study researchers conducted this large prospective study of Mendelian randomization analyzes using data from the UK’s BioBank, a large cohort study of over 500,000 adults (ages 40-69 years) from 2006 to 2010. Of the 408,609 patients examined, 132,566 (32%) were ever regular smoked and 902 (0.22%) were diagnosed with SAH.

A polygenic risk score, representing the genetic tendency to smoke, was established using genetic data at the individual level and comprised 126 single nucleotide polymorphisms.

There was a strong association between genetic susceptibility to smoking and smoking cessation, as well as the risk of SAH. Each additional SD of the polygenic risk score for smoking was associated with a 21 percent increased risk of starting smoking (odds ratio) [OR]1.21; 95% CI, 1.20-1.21; P <0.001) and with a 10 percent increased risk of SAH (OR 1.10; 95% CI 1.03-1.17; P = 0.006).

In the primary Mendelian randomization analysis using the ratio method, genetic susceptibility to smoking was associated with a 63 percent increase in SAH risk (OR 1.63; 95% CI 1.15-2.31; P = 0.006 ). The results were from secondary Mendelian randomization analyzes using the inverse variance-weighted method (OR, 1.57; 95% CI, 1.13-2.17; P = 0.007) and the weighted median method (OR, 1.74 ; 95% CI, 1.06-2.86) similar; P = 0.03).

The results showed that genetic susceptibility to smoking initiation was associated with a 60 percent increase in SAH risk, and when compared to never-smokers, this increased risk was similar for those who took 0.05 to 20 packs per year smoked (OR, 1.63; 95)% CI 1.01-2.62; P = 0.04), 20 to 40 packs per year (OR 1.65; 95% CI 1.13-2.41; P = 0.009) and more than 40 packs per year (OR 1.56; 95)% CI, 1.08-2.25; P = 0.02).

According to the study researchers, the study had several limitations, including a possible misclassification of the result as a result of using ICD codes to determine SAH cases, the lack of an independent dataset to confirm the results, and the limited population of the study population (all) genetic white Study participants). As a result, the results cannot be transferred to other racial and / or ethnic groups.

“We found that a stronger genetic predisposition to smoking is significantly linked to an increased risk of SAH. These results provide important evidence for a causal link between smoking and the risk of SAH, ”the study’s researchers concluded.

Disclosure: Several authors of the study have stated that they are part of the pharmaceutical industry. For a full list of the authors’ information, see the original reference.


Acosta JN, Szejko N., Both CP, et al. Genetically determined smoking behavior and risk of non-traumatic subarachnoid hemorrhage. Stroke. Published online January 14, 2021. doi: 10.1161 / STROKEAHA.120.031622

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