Vikas Pandey, MD

Holliday EG, Traylor M, Malik R, Bevan S, Falcone G, Hopewell JC, et al. Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke. Stroke. 2015

The attributable risk of genetics to the development of ischemic strokes is likely higher than most of us realize. While typical risk factors such as hypertension, dyslipidemia, diabetes and smoking are relatively well-understood, less is known about the role of an individual’s genetic makeup to determine who is at higher risk of suffering an ischemic stroke. As someone who has had two previous generations of family members with “cryptogenic” strokes/thrombosis, the genetics of conditions of hypercoagulability has always interested me. While the connection between different hypercoagulable conditions and ischemic stroke has been more established, reversing the concept by attempting to broadly detect different susceptibility genes for ischemic strokes is one that has proven more difficult due to the presence of pathophysiological differences in ischemic stroke subtypes. 

The multinational group in the article cited decided to analyze genome-wide summary data for 12, 389 ischemic strokes from 15 different studies and divided the patients into three major subtypes of large artery atherosclerosis (LAA: 2,167 patients), cardioembolism (2,405 patients) and small vessel disease (SVD: 1,854 patients). The remainder of the patient’s not classified had other, undetermined or cryptogenic etiologies. There were 62,004 controls. Their goal was to determine if the ischemic stroke subtypes had any genetic overlap to suggest that a specific genetic locus can contribute to more than one ischemic stroke subtype. Statistical analyses used for determining genetic correlations were linear mixed models and polygenic profile scores. They found that there was high genetic correlation between LAA and SVD patients using linear mixed models and specifically there was a strong association in the joint meta-analysis of LAA and SVD near the opioid receptor mu1 (OPRM1) gene.

The study reveals an exciting piece of information that LAA and SVD may have a shared genetic etiology and that these two entities may be more alike than we think. More studies are needed to verify and further clarify this association and these future studies will no doubt provide more information regarding gene function and biological mechanisms that may be shared by these genetic loci, which logically would lead to another proposed channel of treatment of these stroke subtypes. Genetic research is a fundamental component of broadening the field of stroke research and continued discovery into the link of what causes strokes can lead to more effective methods of stroke prevention and treatment.