Genetic Risk Factors for Intracerebral Hemorrhage in East Asian Populations

Introduction: Spontaneous intracerebral hemorrhage (ICH) is a life-threatening neurological emergency with a high mortality rate. The incidence of ICH is notably higher in East Asian populations compared to Caucasians, with hypertension being the most significant risk factor. Additionally, ICH types differ between populations. Lobar ICH, linked to cerebral amyloid angiopathy, is more common in Caucasians, while deep ICH, strongly associated with hypertension, is prevalent in East Asians. This highlights the fact that genetic factors play a crucial role in the pathogenesis of complex diseases. Currently, there are limited large-scale studies examining the genetic risk factors for ICH in East Asian populations. We conducted a GWAS by using a machine-learning method to identify novel genes associated with ICH in Eastern Asian populations.

Methods: Our study conducted a large-scale meta-analysis of genome-wide associated study (GWAS) for ICH to identify novel genetic risk factors and possible biological mechanism for ICH in Eastern Asian population (3,375 cases and 334,926 controls), integrating ICH cohorts from Taiwan and Japan. Two novel independent genomic risk loci on chromosome 4 (4q21.1) and chromosome 12 (12q24.13) had shown genome-wide significance.

Results: Functional annotation and analysis identified four genes: FGF5, HECTD4, PRDM8, and BMP3. Notably, FGF5 and HECTD4 have been associated with hypertension, particularly in Asian populations. Using gene-based analysis for the predicted expression models in tissues, we found that experiment wide significant (p-value < 5 x 10-7) associations at four genes including FGF5 in kidney cortex, ABO in artery coronary.

Conclusion : The findings of our study offer new insights into the genetic basis of ICH in the Asian population and contribute to the development of novel strategies for the prevention and treatment of ICH.