AUTHOR=Lin Forrest , Tomppo Liisa , Gaynor Brady , Ryan Kathleen , Cole John W. , Mitchell Braxton D. , Putaala Jukka , Kittner Steven J. TITLE=Genomic risk scores and oral contraceptive-associated ischemic stroke risk: a call for collaboration JOURNAL=Frontiers in Stroke VOLUME=2 YEAR=2023 URL=https://www.frontiersin.org/journals/stroke/articles/10.3389/fstro.2023.1143372 DOI=10.3389/fstro.2023.1143372 ISSN=2813-3056 ABSTRACT=Background

Oral contraceptives (OCs) are generally safe but vascular risk factors increase OC-associated ischemic stroke risk. We performed a case-control study to evaluate whether a genomic risk score for ischemic stroke modifies OC-associated ischemic stroke risk.

Methods

The Genetics of Early-Onset Stroke study includes 332 premenopausal women (136 arterial ischemic stroke cases and 196 controls) with data on estrogen-containing OC use within 30 days before the index event (for cases) or interview (for controls). Using a previously validated genetic risk score (metaGRS) for ischemic stroke based on 19 polygenic risk scores for stroke and stroke-associated risk factors, we stratified our combined case-control sample into tertiles of genomic risk. We evaluated the association between OC use and ischemic stroke within each tertile. We tested if the association between OC use and ischemic stroke depended on the genomic risk of stroke using logistic regression with an OC use × metaGRS interaction term. These analyses were performed with and without adjustment for smoking, hypertension, diabetes, coronary heart disease, and body mass index.

Results

After adjustment for vascular risk factors, the odds ratio of OC use was 3.2 (1.7–6.3) overall and increased from the lower, middle, and upper tertile of genomic risk from 1.6 (0.5–5.4) to 2.5 (0.08–8.2) to 13.7 (3.8–67.3) respectively, and a p-value for interaction of 0.001.

Conclusions

Our results suggest that genomic profile may modify the OC-associated ischemic stroke risk. Larger studies are warranted to determine whether a genomic risk score could be clinically useful in reducing OC-associated ischemic stroke.