Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics

自闭症谱系障碍 全基因组关联研究 表达数量性状基因座 生物 计算生物学 孟德尔随机化 神经发育障碍 药物数据库 遗传学 生物信息学 药品 医学 自闭症 基因 药理学 单核苷酸多态性 基因型 精神科 遗传变异
作者
Rui Jiang,Wentao Huang,Xinqi Qiu,Jianyi Chen,Ruibang Luo,Ruijie Zeng,Shuangshuang Tong,Yanlin Lyu,Panpan Sun,Qizhou Lian,Felix W. Leung,Yufeng Liu,Weihong Sha,Hao Chen
出处
期刊:Briefings in Bioinformatics [Oxford University Press]
卷期号:25 (4)
标识
DOI:10.1093/bib/bbae353
摘要

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which current treatments are limited and drug development costs are prohibitive. Identifying drug targets for ASD is crucial for the development of targeted therapies. Summary-level data of expression quantitative trait loci obtained from GTEx, protein quantitative trait loci data from the ROSMAP project, and two ASD genome-wide association studies datasets were utilized for discovery and replication. We conducted a combined analysis using Mendelian randomization (MR), transcriptome-wide association studies, Bayesian colocalization, and summary-data-based MR to identify potential therapeutic targets associated with ASD and examine whether there are shared causal variants among them. Furthermore, pathway and drug enrichment analyses were performed to further explore the underlying mechanisms and summarize the current status of pharmacological targets for developing drugs to treat ASD. The protein-protein interaction (PPI) network and mouse knockout models were performed to estimate the effect of therapeutic targets. A total of 17 genes revealed causal associations with ASD and were identified as potential targets for ASD patients. Cathepsin B (CTSB) [odd ratio (OR) = 2.66 95, confidence interval (CI): 1.28-5.52, P = 8.84 × 10-3], gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (OR = 1.99, 95CI: 1.06-3.75, P = 3.24 × 10-2), and formin like 1 (FMNL1) (OR = 0.15, 95CI: 0.04-0.58, P = 5.59 × 10-3) were replicated in the proteome-wide MR analyses. In Drugbank, two potential therapeutic drugs, Acamprosate (GABBR1 inhibitor) and Bryostatin 1 (CASP8 inhibitor), were inferred as potential influencers of autism. Knockout mouse models suggested the involvement of the CASP8, GABBR1, and PLEKHM1 genes in neurological processes. Our findings suggest 17 candidate therapeutic targets for ASD and provide novel drug targets for therapy development and critical drug repurposing opportunities.
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
小马甲应助不站在雾里采纳,获得10
刚刚
pp完成签到 ,获得积分0
1秒前
zhangjianzeng完成签到 ,获得积分10
1秒前
史小菜应助云轩采纳,获得20
2秒前
伏伏雅逸发布了新的文献求助10
2秒前
李健应助荒野风采纳,获得10
3秒前
Popeye应助单纯血茗采纳,获得10
3秒前
淡然冬灵发布了新的文献求助10
3秒前
Popeye应助单纯血茗采纳,获得10
3秒前
荔枝的油饼iKun完成签到,获得积分10
4秒前
Bosen完成签到,获得积分10
4秒前
Astraeus完成签到 ,获得积分10
5秒前
fengyuenanche完成签到,获得积分10
6秒前
五虎完成签到,获得积分10
7秒前
Akim应助Rollei采纳,获得10
8秒前
hoshi1018完成签到,获得积分10
9秒前
友好曲奇完成签到,获得积分10
9秒前
dongdong完成签到 ,获得积分10
10秒前
CR7完成签到,获得积分0
11秒前
左丘忻完成签到,获得积分10
11秒前
凤迎雪飘完成签到,获得积分10
11秒前
11秒前
FashionBoy应助云轩采纳,获得10
12秒前
领导范儿应助伏伏雅逸采纳,获得10
12秒前
13秒前
Rondab应助悦耳荟采纳,获得10
13秒前
liqian完成签到,获得积分10
13秒前
易安发布了新的文献求助100
14秒前
15秒前
完美世界应助科研通管家采纳,获得10
15秒前
852应助科研通管家采纳,获得10
15秒前
今后应助科研通管家采纳,获得10
15秒前
cdh1994应助科研通管家采纳,获得10
15秒前
英姑应助科研通管家采纳,获得10
15秒前
沉默的谷秋完成签到,获得积分10
15秒前
大个应助科研通管家采纳,获得10
15秒前
过时的热狗完成签到,获得积分10
16秒前
16秒前
上官若男应助科研通管家采纳,获得10
16秒前
16秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
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 4038446
求助须知:如何正确求助?哪些是违规求助? 3576149
关于积分的说明 11374627
捐赠科研通 3305875
什么是DOI,文献DOI怎么找? 1819354
邀请新用户注册赠送积分活动 892680
科研通“疑难数据库(出版商)”最低求助积分说明 815048