BMC MED:体检报告中的“腔隙性脑梗死”,居然可能是个基因病?!这些位点可能与之相关!

2022-06-28 网络 网络

ICA1L、CAND2和ALDH2是引人注目的基因,可能为未来的功能研究和腔隙性脑梗的可能治疗目标提供关键提示。

以前的全基因组关联研究(GWAS)已经确定了许多腔隙性脑梗的风险基因,但要破译它们如何赋予疾病的风险是具有挑战性的。为此,来自浙江大学的学者采用了一个综合分析管道来有效地转化基因关联,以确定腔梗相关的新型蛋白质。结果发表在BMC MEDICINE杂志上。

研究人员系统地将腔隙性脑梗全基因组关联研究(GWAS)(N=7338)与人脑蛋白组(N=376)结合起来,进行全蛋白组关联研究(PWAS)、孟德尔随机化(MR)和贝叶斯同源化。随后还使用一个独立的人脑蛋白质组数据集(N=152)来注释新的基因。

结果显示,共发现七个基因(ICA1L、CAND2、ALDH2、MADD、MRVI1、CSPG4和PTPN11)在大脑中的蛋白丰度与腔隙性脑梗有关。这七个基因主要表达在谷氨酸神经元、GABA能神经元和星形胶质细胞的表面。三个基因(ICA1L、CAND2、ALDH2)在腔隙性脑梗中具有因果关系(P<0.05/PWAS鉴定的蛋白质;贝叶斯同位素的假设4的后验概率≥75%),在确认性PWAS和独立的MR中它们与腔隙性脑梗有关。此外,还发现ICA1L在脑部转录组水平上与腔隙性脑梗有关。

综上,目前的蛋白质组学研究结果发现ICA1L、CAND2和ALDH2是引人注目的基因,可能为未来的功能研究和腔隙性脑梗的可能治疗目标提供关键提示。

 

参考文献:

Identification of novel proteins for lacunar stroke by integrating genome-wide association data and human brain proteomes. BMC Med 20, 211 (2022). https://doi.org/10.1186/s12916-022-02408-y

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    2022-06-27 marongnuan
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    2022-06-27 karmond
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