Trans-ethnic Meta-analysis of Vitamin D Receptor Gene Variants in Context of Polygenic Risk, Associated with Difference in Incidence of Hypertension-Mediated Intracerebral Hemorrhage Across Ethnic Groups

Abstract

Stroke is second in rates of mortality experienced globally (Katan & Luft, 2018). Defined by a bleed or blockage of a blood vessel in the brain, ischemic and hemorrhagic strokes, respectively, are the two primary types (Katan & Luft, 2018). Hemorrhagic stroke is responsible for the most mortality and disease burden. Post-Hemorrhagic stroke disability often includes declines in cognition, behavior, and motor functions (Dajpratham et al., 2020). As with other diseases, stroke is twice as likely to occur in people of color, Black/African Americans especially. The same can be said for hypertension, which is also a prime risk factor for the incidence of hemorrhagic stroke (Girouard & Ladecola, 2006). Allocation of genomic profiles via genome-wide association studies (GWAS) have allowed for ethnicity-based assessment of hypertension-mediated intracerebral hemorrhage (ICH), as influenced by Vitamin D receptor (VDR) gene variants, a novel genetic constituent with believed connection to hypertension (Maciejewski et al., 2019). In this thesis, we investigated hemorrhagic stroke’s genetic correlates was addressed with polygenic risk scores tailored to hypertension-mediated ICH as influenced by VDR gene variants. Though statistically insignificant, possibly a result of a lack of representation of black subjects, findings showed increased incidence of hypertension-mediated ICH in black subjects, non-lobar subtype of ICH, consistent with regions where systolic blood pressure polygenic risk scores would have more effect in. Future inquiry into VDR genes and other novel genetic considerations would be beneficial especially when aligned with addressing disparities in disease burden and mortality.