Smoking may be linked to risk for subarachnoid hemorrhage
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Research published in Stroke indicated a causal association between smoking and risk for nontraumatic subarachnoid hemorrhage among individuals of European descent in Britain.
“Our results provide justification for future studies to focus on evaluating whether information on genetic variants leading to smoking can be used to better identify people at high risk of having one of these types of brain hemorrhages,” Julian N. Acosta, MD, neurologist and postdoctoral research fellow at the Yale School of Medicine, said in a press release. “These targeted populations might benefit from aggressive diagnostic interventions that could lead to early identification of the aneurysms that cause this serious type of bleeding stroke.”
Mendelian randomization
For this analysis, researchers performed a one-sample Mendelian randomization study using data from the UK Biobank and included 408,609 participants (mean age, 57 years; 54% women) with the aim to establish a causal relationship between smoking and risk for nontraumatic subarachnoid hemorrhage.
Cases of subarachnoid hemorrhage were gathered using self-reported, electronic medical record and death registry data. Researchers used this information, in addition to known independent genetic variants associated with smoking behavior, to build a polygenic risk score that represented an individual’s susceptibility to smoking initiation.
“Previous studies have shown that smoking is associated with higher risks of subarachnoid hemorrhage, yet it has been unclear if smoking or another confounding condition such as high blood pressure was a cause of the stroke,” Guido Falcone, MD, ScD, MPH, assistant professor of neurology at the Yale School of Medicine, said in the release. “A definitive, causal relationship between smoking and the risk of subarachnoid hemorrhage has not been previously established as it has been with other types of stroke.”
In the overall cohort, 32% of participants ever smoked regularly and 0.22% experienced a subarachnoid hemorrhage.
Researchers found that for each additional standard deviation of the smoking polygenic risk score, the risk for smoking initiation increased by 21% (OR = 1.21; 95% CI, 1.2-1.21; P < .001) and the risk for subarachnoid hemorrhage increased by 10% (OR = 1.1; 95% CI, 1.03-1.17; P = .006).
Smoking and hemorrhage risk
In the Mendelian randomization analysis, genetic susceptibility to smoking was associated with a 63% increased risk for subarachnoid hemorrhage (OR = 1.63; 95% CI, 1.15-2.31; P = .006).
In both the polygenic risk score analyses and the Mendelian randomization, sex (P for interaction = .22) and hypertension (P for interaction = .49) did not affect the results.
Secondary analyses that applied the inverse variance weighted and weighted median methods demonstrated similar findings (OR for inverse variance weighted = 1.57; 95% CI, 1.13-2.17; P = .007; OR for weighted median = 1.74; 95% CI, 1.06-2.86; P = .03).
“Deriving causality from observational evidence is problematic because of the possibility of bias introduced by confounding factors. Addressing this question through experimental studies in humans (ie, randomized clinical trials) would be unethical given the known harms produced by smoking,” Acosta and colleagues wrote. “Population genetics provides powerful tools to overcome these limitations in causal inference.”
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