Association between genetic predisposition and disease burden of stroke in China: a genetic epidemiological study

Stroke ranks second worldwide and first in China as a leading cause of death and disability. It has a polygenic architecture and is influenced by environmental and lifestyle factors. However, it remains unknown as to whether and how much the genetic predisposition of stroke is associated with disease burden.

Allele frequency from the whole genome sequencing data in the Chinese Millionome Database of 141,418 individuals and trait-specific polygenic risk score models were applied to estimate the provincial genetic predisposition to stroke, stroke-related risk factors and stroke-related drug response. Disease burden including mortality, disability-adjusted life years (DALYs), years of life lost(YLLs), years lived with disability (YLDs) and prevalence in China was collected from the Global Burden Disease study. The association between stroke genetic predisposition and the epidemiological burden was assessed and then quantified in both regression-based models and machine learning-based models at a provincial resolution.

Among the 30 administrative divisions in China, the genetic predisposition of stroke was characterized by a north-higher-than-south gradient (p < 0.0001). Genetic predisposition to stroke, blood pressure, body mass index, and alcohol use were strongly intercorrelated (rho >0.6; p < 0.05 after Bonferroni correction for each comparison). Genetic risk imposed an independent effect of approximately 1-6% on mortality, DALYs and YLLs.

The distribution pattern of stroke genetic predisposition is different at a macroscopic level, and it subtly but significantly impacts the epidemiological burden. Further research is warranted to identify the detailed aetiology and potential translation into public health measures.

Beijing Municipal Science and Technology Commission (Z191100006619106), CAMS Innovation Fund for Medical Sciences (CAMS-I2M, 2023-I2M-1-001), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17), National Natural Science Foundation of China (32000398, 32171441 to X.J.), Natural Science Foundation of Guangdong Province, China (2017A030306026 to X.J.), and National Key R&D Program of China (2022YFC2502402).