Abstract WMP108: Genomic Risk Scores And Oral Contraceptive-associated Ischemic Stroke Risk

Objective: To evaluate whether a genomic risk score for ischemic stroke (IS) modifies oral contraceptive (OC)-associated IS risk. Background: OCs are generally safe but vascular risk factors are known to increase OC-associated IS risk. If a genomic risk score could identify a subset of women with substantially increased risk of OC-associated IS, this could influence prescribing guidelines and reduce stroke events. Methods: In the Genetics of Early-Onset Stroke (GEOS) study, there were 340 premenopausal women (143 IS cases and 197 controls) with data on OC use within 30 days prior to index event for cases or prior to interview for controls. Using a previously validated genomic risk score (metaGRS) for IS based on 19 polygenic risk scores of vascular events and risk factors, we stratified our sample into tertiles of genomic risk and calculated the association between OC use and IS within each tertile. We tested if the association between OC use and IS depended on genomic risk of stroke using logistic regression with an OC use*metaGRS interaction term. Results: Among all women, OC use was significantly associated with IS (odds ratio = 2.4, p = 0.002). The odds ratio for IS associated with OC use decreased from 3.9 in the tertile with highest genomic risk of IS to 1.5 in the tertile with lowest genomic risk (see Table). The formal test of interaction was consistent with our hypothesis (p = 0.07) that the genomic risk score modifies the association of OC use with IS. Conclusions: The results of our exploratory analysis support the need for international collaboration to generate sufficient sample sizes to determine whether a genomic risk score could be clinically useful in reducing OC-associated IS.