The Association Between Smoking and Subarachnoid Hemorrhage

covid-19,Close-up of man with medical mask smoking a cigarette at the street
Researchers assessed the relationship between smoking and non-traumatic subarachnoid hemorrhage.

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

Data suggest that smoking is an important risk factor for aneurysm formation and rupture. While previous studies have identified an increased risk for non-traumatic SAH among smokers, the causal association is not well understood.  The objective of this study was to determine if smoking is causally related to the risk for SAH.

Study researchers conducted this large prospective study with Mendelian Randomization analyses using data from the UK BioBank, a large cohort study with over 500,000 adults (age, 40-69 years) from 2006 to 2010. Of the 408,609 patients evaluated, 132,566 (32%) ever smoked regularly and 902 (0.22%) were diagnosed with SAH.

A polygenic risk score that represents the genetic propensity to smoke was built using individual-level genetic data and included 126 single nucleotide polymorphisms.

There was a strong association between genetic susceptibility to smoking with both smoking initiation and risk of SAH. Each additional SD of the smoking polygenic risk score was associated with a 21 percent increased risk for smoking initiation (odds ratio [OR], 1.21; 95% CI, 1.20-1.21; P <.001) and with a 10 percent increased risk for SAH (OR, 1.10; 95% CI, 1.03-1.17; P =.006).

In the primary Mendelian Randomization analysis using the ratio method, genetic susceptibility to smoking was linked to a 63 percent increase in risk of SAH (OR, 1.63; 95% CI, 1.15-2.31; P =.006). The results were similar on secondary Mendelian Randomization analyses using the inverse variance weighted method (OR, 1.57; 95% CI, 1.13-2.17; P =.007) and the weighted median method (OR, 1.74; 95% CI, 1.06-2.86; P =.03).

Findings indicated that the genetic susceptibility to smoking initiation was associated with a 60 percent increase in the risk of SAH, and, compared with never smokers, this increased risk was similar for those who smoked 0.05 to 20 packs per year (OR, 1.63; 95% CI, 1.01-2.62; P =.04), 20 to 40 packs per year (OR, 1.65; 95% CI, 1.13-2.41; P =.009) and more than 40 packs per year (OR, 1.56; 95% CI, 1.08-2.25; P =.02).

The study had several limitations, according to the study researchers, including potential misclassification of the outcome secondary to use of ICD codes to determine SAH cases, the absence of an independent dataset to confirm the results, and the limited demographic of the study population (all genetically determined White study participants). As a result, findings cannot be applied to other racial and/or ethnic populations.

“We found that a stronger genetic predisposition to smoking is significantly associated with an increased risk of SAH. These findings provide important evidence to support a causal relationship between smoking and the risk of SAH,” concluded the study researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


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