Wang Pei, Yao Ming, Yuan Jing, Han Fei, Zhai Fei-Fei, Zhang Ding-Ding, Zhou Li-Xin, Ni Jun, Zhang Shu-Yang, Cui Li-Ying, Zhu Yi-Cheng
Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
J Am Heart Assoc. 2024 Feb 20;13(4):e032668. doi: 10.1161/JAHA.123.032668. Epub 2024 Feb 13.
It is uncertain whether rare variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare variants with prevalent and incident stroke and dementia, as well as cognitive function changes.
In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare variants were defined as variants with minor allele frequency <1%. A total of 137 rare carriers were enrolled in the baseline study. At baseline, rare variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; =0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; =0.032). After 5 years of follow-up, we did not find that the rare variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores.
Rare EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.
在普通人群中，罕见变异是否与中风和痴呆相关，以及它们是否会导致认知功能改变尚不确定。本研究旨在确定罕见变异与中风和痴呆的患病率及发病率以及认知功能变化之间的关联。
在基于社区的前瞻性顺义研究中，共有1007名参与者纳入基线分析。在随访分析中，1007名参与者纳入中风分析，870名参与者纳入痴呆分析。所有参与者均接受了基线脑磁共振成像、颈动脉超声检查和全外显子测序。罕见变异定义为次要等位基因频率<1%的变异。共有137名罕见变异携带者纳入基线研究。在基线时，与非携带者相比，罕见变异携带者的中风发生率（8.8%对5.6%）和痴呆发生率（2.9%对0.8%）更高。在对相关危险因素进行校正后，涉及表皮生长因子样重复序列（EGFr）的罕见变异与中风患病率较高风险相关（比值比[OR]，2.697[95%置信区间，1.266 - 5.745]；P = 0.040）以及痴呆（OR，8.498[95%置信区间，1.727 - 41.812]；P = 0.032）。经过5年随访，我们未发现罕见变异增加中风和痴呆的发病风险。纵向认知量表评分变化无统计学差异。
在中国普通人群中，涉及EGFr的罕见变异是中风和痴呆的遗传危险因素。
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