Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression-Quantitative Trait Loci

生物 表达数量性状基因座 基因 哮喘 反褶积 电池类型 数量性状位点 特质 基因表达 计算生物学 遗传学 细胞 基因型 免疫学 计算机科学 算法 单核苷酸多态性 程序设计语言
作者
Zaid W. El‐Husseini,Tatiana Karp,Andy Lan,Tessa E. Gillett,Cancan Qi,Dmitry Khalenkow,Thys van der Molen,Christopher E. Brightling,Alberto Papi,Klaus F. Rabe,Salman Siddiqui,Dave Singh,Monica Kraft,Bianca Beghè,Philippe Joubert,Yohan Bossé,Don D. Sin,A. Hernandez Cordero,Wim Timens,Corry‐Anke Brandsma,Ke Hao,David C. Nickle,Judith M. Vonk,Martijn C. Nawijn,Maarten van den Berge,Reinoud Gosens,Alen Faiz,Gerard H. Koppelman
出处
期刊:American Journal of Respiratory Cell and Molecular Biology [American Thoracic Society]
标识
DOI:10.1165/rcmb.2024-0251ma
摘要

Asthma is a genetically complex inflammatory airway disease associated with over 200 Single nucleotide polymorphisms (SNPs). However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples. We hypothesize that incorporating cell-type proportions of airway and lung samples enhances eQTL analysis outcomes. Nasal brush (n=792) and lung tissue (n=1087) samples were investigated separately. Initially, a general eQTL analysis identified genetic variants associated with gene expression levels. Estimated cell-type proportions were adjusted based on the Human Lung Cell Atlas. Additionally, the presence of significant interaction effects between asthma-associated SNPs and each cell type proportion was explored and considered evidence for cell-type associated eQTL. In nasal brush and lung parenchyma samples, 44 and 116 asthma-associated SNPs were identified as eQTLs. Adjusting for cell-type proportions revealed eQTLs for an additional 17 genes (e.g., FCER1G, CD200R1, and GABBR2) and 16 Genes (e.g., CYP2C8, SLC9A2, and SGCD) in nose and lung, respectively. Moreover, we identified eQTLs for 9 SNPs annotated to genes such as VASP, FOXA3, PCDHB12 displayed significant interactions with cell type proportions of Club, Goblet, and alveolar macrophages. Our findings demonstrate increased power for identifying eQTLs among asthma-associated SNPs by considering cell-type proportion of the bulk-RNA-seq data from nasal and lung tissues. Integration of cell-type deconvolution and eQTL analysis enhances our understanding of asthma genetics and cellular mechanisms, uncovering potential therapeutic targets for personalized interventions.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
刚刚
1秒前
ddd发布了新的文献求助10
3秒前
meng发布了新的文献求助10
3秒前
熠旅发布了新的文献求助10
4秒前
55555发布了新的文献求助10
4秒前
sutharsons应助科研通管家采纳,获得30
5秒前
搜集达人应助科研通管家采纳,获得10
5秒前
天天快乐应助科研通管家采纳,获得10
5秒前
华仔应助科研通管家采纳,获得10
5秒前
5秒前
5秒前
5秒前
深情安青应助科研通管家采纳,获得10
6秒前
打打应助科研通管家采纳,获得10
6秒前
彭于晏应助科研通管家采纳,获得10
6秒前
sutharsons应助科研通管家采纳,获得30
6秒前
7秒前
7秒前
123发布了新的文献求助10
9秒前
10秒前
violin发布了新的文献求助10
10秒前
勇往直前发布了新的文献求助10
11秒前
山山而川应助ddd采纳,获得30
14秒前
zho关闭了zho文献求助
14秒前
拣尽南枝完成签到 ,获得积分10
15秒前
lwroche发布了新的文献求助10
16秒前
隐形曼青应助雷小仙儿采纳,获得10
17秒前
充电宝应助123采纳,获得10
18秒前
悦耳冬萱完成签到 ,获得积分10
21秒前
22秒前
22秒前
23秒前
24秒前
WANG发布了新的文献求助10
26秒前
28秒前
Jasper应助依然灬聆听采纳,获得10
29秒前
29秒前
淡然平灵发布了新的文献求助10
30秒前
youngneuron发布了新的文献求助10
30秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2000
Very-high-order BVD Schemes Using β-variable THINC Method 1200
奈特消化系统医学图谱(第2版) 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 1000
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 1000
中国荞麦品种志 1000
BIOLOGY OF NON-CHORDATES 1000
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3360706
求助须知:如何正确求助?哪些是违规求助? 2982987
关于积分的说明 8706327
捐赠科研通 2664776
什么是DOI,文献DOI怎么找? 1459389
科研通“疑难数据库(出版商)”最低求助积分说明 675426
邀请新用户注册赠送积分活动 666517