Hong Eun Pyo, Lim Seung Hyuk, Youn Dong Hyuk, Han Sung Woo, Jung Harry, Lee Jae Jun, Jeon Jin Pyeong
Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24254, Republic of Korea.
Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea.
Biomedicines. 2024 Jun 22;12(7):1387. doi: 10.3390/biomedicines12071387.
The occurrence of cognitive deficits after subarachnoid hemorrhage (SAH) is highly possible, leading to vascular dementia. We performed a novel longitudinal genome-wide association study (GWAS) to identify genetic modifications associated with cognitive impairment following SAH in a long-term prospective cohort study.
This GWAS involved 153 patients with SAH sharing 5,971,372 markers after high-throughput imputation. Genome-wide Cox proportional hazard regression testing was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Subsequently, a weighted polygenetic risk score (wPRS) was determined, based on GWAS-driven loci and risk stratification.
Cognitive impairment was observed in 65 patients (42.5%) during a mean follow-up of 37.7 ± 12.4 months. Five genome-wide signals, including rs138753053 (-, HR = 28.33, = 3.4 × 10), rs56823384 (, HR = 12.47, = 2.8 × 10), rs145397166 (, HR = 11.16, = 1.7 × 10), rs10503670 (-, HR = 2.88, = 4.0 × 10), and rs76507772 (, HR = 5.99, = 3.5 × 10), were significantly associated with cognitive impairment following SAH. In addition, the well-constructed wPRS containing five markers showed nominal ability to predict cognitive impairment (AUROC = 0.745, 95% CI: 0.667-0.824). Tertile stratification showed a higher effectiveness in predicting cognitive impairment, especially in those with haptoglobin 2-1 (HR = 44.59, 95% CI: 8.61-231.08).
Our study revealed novel susceptible loci for cognitive impairment, longitudinally measured in patients with SAH. The clinical utility of these loci will be evaluated in further follow-up studies.
蛛网膜下腔出血（SAH）后极有可能出现认知缺陷，进而导致血管性痴呆。我们开展了一项全新的纵向全基因组关联研究（GWAS），旨在通过一项长期前瞻性队列研究，确定与SAH后认知障碍相关的基因改变。
这项GWAS纳入了153例SAH患者，经过高通量插补后共有5,971,372个标记。进行全基因组Cox比例风险回归测试，以估计风险比（HR）和95%置信区间（CI）。随后，基于GWAS驱动的基因座和风险分层确定加权多基因风险评分（wPRS）。
在平均37.7±12.4个月的随访期间，65例患者（42.5%）出现认知障碍。五个全基因组信号，包括rs138753053（-，HR = 28.33，= 3.4×10）、rs56823384（，HR = 12.47，= 2.8×10）、rs145397166（，HR = 11.16，= 1.7×10）、rs10503670（-，HR = 2.88，= 4.0×10）和rs76507772（，HR = 5.99，= 3.5×10），与SAH后的认知障碍显著相关。此外，包含五个标记的构建良好的wPRS显示出预测认知障碍的标称能力（AUROC = 0.745，95% CI：0.667 - 0.824）。三分位数分层在预测认知障碍方面显示出更高的有效性，尤其是在触珠蛋白2 - 1的患者中（HR = 44.59，95% CI：8.61 - 231.08）。
我们的研究揭示了SAH患者纵向测量的认知障碍新的易感基因座。这些基因座的临床效用将在进一步的随访研究中进行评估。
