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Abstract Details

Genetic Analyses Support a Causal Role of Lung Cancer in Ischemic Stroke
Cerebrovascular Disease and Interventional Neurology
S33 - Cerebrovascular Disease: Basic Sciences and Cohort Studies (5:18 PM-5:30 PM)
010
Lung cancer has been linked to increased risk of ischemic stroke (IS). However, a causal relationship between the two has yet to be established.
To evaluate the relationship between lung cancer and ischemic stroke.

We analyzed data from the UK Biobank, a large cohort study that enrolled over 500,000 Britons aged 40-69. We included participants of European ancestry. First, we used logistic regression to test the association between self-reported/ICD-defined lung cancer and risk of IS. Then, we constructed a polygenic risk score (PRS) using 31 independent genetic variants known to associate with lung cancer, fitted logistic regression to assess the relationship between this PRS and risk of IS, and implemented the inverse variance weighted method of Mendelian randomization (MR). We tested for horizontal pleiotropy using the MR-Egger and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) approaches.

Out of 409,629 participants of European ancestry in the UK Biobank, there were 5,060 IS cases (mean age, 61.6 [standard deviation 6.5]; female, 1,813 [35.8%]). The prevalence of lung cancer was 1.9% (n=94) and 0.5% (n=1,961) among persons with and without IS, respectively (unadjusted p<0.001). In multivariate analysis, self-reported/ICD-defined lung cancer was associated with 54% higher odds of IS (OR, 1.54; 95% CI, 1.30-1.81; p<0.001). Genetic analyses supported a causal link between lung cancer and IS. In PRS analysis, each additional standard deviation of the lung cancer-related PRS was associated with 3% higher odds of IS (adjusted OR, 1.03; 95% CI, 1.01-1.06; p=0.018). In MR analysis, genetically determined lung cancer was associated with 5% higher odds of IS (OR, 1.05; 95% CI, 1.01-1.09; p=0.022). There was no significant horizontal pleiotropy (MR-Egger intercept p=0.663; MR-PRESSO global test p=0.993).

Genetically determined lung cancer is associated with increased risk of ischemic stroke. These findings provide evidence for a causal link between lung cancer and ischemic stroke.
Authors/Disclosures
Kevin Vanent
PRESENTER
Mr. Vanent has nothing to disclose.
Julian Acosta (Yale) Dr. Acosta has nothing to disclose.
No disclosure on file
Audrey Leasure Ms. Leasure has nothing to disclose.
Victor Torres-Lopez (Yale University) Mr. Torres-Lopez has nothing to disclose.
Natalia Szejko (University of Calgary) Dr. Szejko has nothing to disclose.
Cyprien Rivier (Yale University) Dr. Rivier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pyxis Partners.
Adam De Havenon (Yale University) Dr. De Havenon has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. De Havenon has stock in Certus. Dr. De Havenon has stock in TitinKM. The institution of Dr. De Havenon has received research support from NIH/NINDS. Dr. De Havenon has received publishing royalties from a publication relating to health care.
Richa Sharma (Massachusetts General Hospital, Brigham, Harvard) Dr. Sharma has received research support from NIH. Dr. Sharma has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Kevin Sheth (Yale UniversityDivision of Neuro and Critical Care) Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care.
Guido Falcone (Yale School of Medicine) The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.