Genetic predisposition to diabetes and risk of stroke in a Native Hawaiian population

Diabetes is a highly heritable risk factor for stroke, with many known genetic variants. The role of these genetic variants in cerebrovascular disease has not been studied in Kānaka Maoli (Native Hawaiian) populations. We aimed to determine if genetic predisposition to diabetes is associated with a higher risk of stroke in a Kānaka Maoli population.

We conducted a genetic association case/control study using data from Kānaka Maoli participants in the Population Architecture using Genomics and Epidemiology (PAGE) study. Stroke cases were identified through health questionnaires and matched by age and sex at a 1:10 ratio. We modeled genetic predisposition to diabetes with a polygenic risk score that included independent genetic variants known to be associated with diabetes at a genome-wide significance level (p < 5 × 10⁸). This polygenic risk score served as the independent variable in logistic regression models for both diabetes and stroke.

A total of 440 Kānaka Maoli individuals were included (15% under 50 years old, 85% aged 50-69, 65% female). There were 40 stroke patients and 400 age- and sex-matched control subjects. Genetic predisposition to diabetes was linked to a 23% increased risk of developing diabetes (OR 1.23, CI 1.01-1.51; p = 0.04) and a 45% increased risk of stroke (OR 1.45, CI 1.03-2.05; p = 0.04).

In a Kānaka Maoli population, genetic predisposition to diabetes is associated with an increased risk of stroke. Future research to identify effect modifiers of this relationship may uncover significant public health strategies.