Genome-wide genetic overlap analysis of the genetic contribution shared between stroke and trouble falling asleep, with cross-ethnic validation

Epidemiological studies show a correlation, but the genetic mechanisms remain unclear. We combined large-scale GWAS summary statistics with clinical cohort data from an Asian population for validation, and used the MiXeR model to assess the polygenic overlap between the two traits. CondFDR/conjFDR analyses were used to identify novel loci, and then these were validated by multivariable logistic regression and TWAS.

The results indicated that there was substantial overlap in polygenic signals, with approximately 393 shared genetic variants identified. Clinical data showed that 46.7% of stroke patients experienced trouble falling asleep. Male sex, hemorrhagic stroke, and a history of hypertension were all independent risk factors.

TWAS using the S-PrediXcan method identified four genes (ALDH2, TWIST1, ARL17A, and LRRC37A2) that may contribute to susceptibility to both stroke and trouble falling asleep. These findings suggest substantial shared genetic architecture between stroke and difficulty initiating sleep, highlighting potential pleiotropic loci that may inform future mechanistic studies and risk stratification. This study was financially supported by the 2023 General Guidance Scientific Research Program of the Health Commission of Hunan Province (Grant No. 202314019315).

Huiying Liu and Shuangqin Chen are contributed equally to this work. School of Nursing, University of South China, No. 28 Changsheng West Road, Zhengxiang District, Hengyang, 421001, Hunan, China Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China Audit and Supervision Headquarters, Sany Heavy Industry Co., Ltd.,, Changsha, 410100, Hunan, China The First Affiliated Hospital, Hengyang Medical School, University of South China, , Hengyang, 421001, Hunan, China The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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