Identifying novel risk genes in intracranial aneurysm by integrating human proteomes and genetics

基因 生物 孟德尔随机化 转录组 全基因组关联研究 计算生物学 蛋白质组 遗传学 候选基因 遗传关联 基因表达 单核苷酸多态性 遗传变异 基因型
作者
Congyan Wu,Hanchen Liu,Qiao Zuo,Aimin Jiang,Chuanchuan Wang,Nan Lv,Ruyue Lin,Yonghui Wang,Kang Zong,Yanpeng Wei,Qinghai Huang,Qiang Li,Pengfei Yang,Rui Zhao,Jianmin Liu
出处
期刊:Brain [Oxford University Press]
卷期号:147 (8): 2817-2825 被引量:5
标识
DOI:10.1093/brain/awae111
摘要

Abstract Genome-wide association studies (GWAS) have become increasingly popular for detecting numerous loci associated with intracranial aneurysm (IA), but how these loci function remains unclear. In this study, we employed an integrative analytical pipeline to efficiently transform genetic associations and identify novel genes for IA. Using multidimensional high-throughput data, we integrated proteome-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR) and Bayesian co-localization analyses to prioritize genes that can increase IA risk by altering their expression and protein abundances in the brain and blood. Moreover, single-cell RNA sequencing (scRNA-seq) of the circle of Willis was performed to enrich filtered genes in cells, and gene set enrichment analysis (GSEA) was conducted for each gene using bulk RNA-seq data for IA. No significant genes with cis-regulated plasma protein levels were proven to be associated with IA. The protein abundances of five genes in the brain were found to be associated with IA. According to cellular enrichment analysis, these five genes were expressed mainly in the endothelium, fibroblasts and vascular smooth muscle cells. Only three genes, CNNM2, GPRIN3 and UFL1, passed MR and Bayesian co-localization analyses. While UFL1 was not validated in confirmation PWAS as it was not profiled, it was validated in TWAS. GSEA suggested these three genes are associated with the cell cycle. In addition, the protein abundance of CNNM2 was found to be associated with IA rupture (based on PWAS, MR and co-localization analyses). Our findings indicated that CNNM2, GPRIN3 and UFL1 (CNNM2 correlated with IA rupture) are potential IA risk genes that may provide a broad hint for future research on possible mechanisms and therapeutic targets for IA.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
脑洞疼应助闾丘山菡采纳,获得10
刚刚
江筱筱完成签到,获得积分10
1秒前
天真之桃完成签到,获得积分10
2秒前
4秒前
Dmooou完成签到,获得积分10
5秒前
5秒前
8秒前
Rondab应助勤恳的夏之采纳,获得10
9秒前
10秒前
trocars发布了新的文献求助10
10秒前
Amos完成签到,获得积分10
11秒前
Rondab应助WQ采纳,获得10
11秒前
坚定的芷珊完成签到,获得积分10
11秒前
zedhumble发布了新的文献求助10
13秒前
大罗发布了新的文献求助10
14秒前
小豆包发布了新的文献求助30
16秒前
16秒前
17秒前
19秒前
22秒前
Meyako完成签到 ,获得积分10
23秒前
Quinna发布了新的文献求助10
23秒前
小豆包完成签到,获得积分20
25秒前
mingming发布了新的文献求助10
25秒前
会撒娇的定帮完成签到 ,获得积分10
27秒前
求知完成签到 ,获得积分10
28秒前
所所应助俏皮的白柏采纳,获得10
29秒前
无情的匪发布了新的文献求助10
29秒前
充电宝应助024680采纳,获得10
30秒前
JamesPei应助mingming采纳,获得10
31秒前
赘婿应助山谷采纳,获得10
31秒前
科研达人发布了新的文献求助10
32秒前
聪慧的梦安完成签到,获得积分10
34秒前
小蘑菇应助甲醇杀手采纳,获得10
34秒前
37秒前
黄黄完成签到,获得积分20
38秒前
39秒前
肖肖发布了新的文献求助10
41秒前
44秒前
善学以致用应助黄黄采纳,获得10
45秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988997
求助须知:如何正确求助?哪些是违规求助? 3531351
关于积分的说明 11253520
捐赠科研通 3269928
什么是DOI,文献DOI怎么找? 1804830
邀请新用户注册赠送积分活动 882063
科研通“疑难数据库(出版商)”最低求助积分说明 809068