Abstract TP248: Genetic Predisposition to Diabetes and Risk of Stroke in Native Hawaiians

Abstract

Background: Diabetes is a highly heritable stroke risk factor with numerous known genetic risk variants. However, the role of these genetic risk variants in the development of cerebrovascular disease in Native Hawaiians remains unknown. We sought to determine whether genetic predisposition to diabetes is associated with higher risk of stroke in a Native Hawaiian population. Methods: We conducted a genetic association case/control study using data from Native Hawaiians enrolled in the Population Architecture using Genomics and Epidemiology (PAGE) study. Stroke cases were ascertained by baseline questionnaires and matched by age and sex in a 1:10 ratio. We modeled genetic predisposition to diabetes through a polygenic risk score that contained independent genetic variants known to associate with diabetes at genome-wide levels (p<5x10 -8 ). This polygenic risk score became the independent variable of logistic regression models for both diabetes and stroke. Results: A total of 440 self-identified Native Hawaiians were included (15% < 50 years of age, 85% ages 50-69, 65% females), including 40 stroke patients and 400 age/sex-matched control subjects. Genetic predisposition to diabetes was associated with a 23% higher risk of diabetes (OR 1.23, CI 1.01-1.51; p=0.04) and with a 45% higher risk of stroke (OR 1.45, CI 1.03-2.05; p=0.04). Conclusions: Among Native Hawaiians, genetic predisposition to diabetes is associated with higher risk of stroke. As research aimed at evaluating the role of polygenic risk data in clinical practice grows rapidly, our results emphasize the importance of including Native Hawaiians in order to avoid health disparities exacerbated by incomplete representation.