Whole-Blood RNA Profiles Associated with Pulmonary Arterial Hypertension and Clinical Outcome

医学 心脏病学 肺动脉高压 内科学 动脉血 血压 重症监护医学
作者
Christopher J. Rhodes,Pablo Otero-Núñez,John Wharton,Emilia M. Swietlik,Sokratis Kariotis,Lars Harbaum,Mark J Dunning,Jason M. Elinoff,Niamh Errington,A. A. Roger Thompson,James Iremonger,J. Gerry Coghlan,Paul A. Corris,Luke Howard,David G. Kiely,Colin Church,Joanna Pepke-Zaba,Mark Toshner,Stephen J. Wort,Ankit A. Desai,Marc Humbert,William C. Nichols,Laura Southgate,David-Alexandre Trégouët,Richard C. Trembath,Inga Prokopenko,Stefan Gräf,Nicholas W. Morrell,Dennis Wang,Allan Lawrie,Martin R. Wilkins
出处
期刊:American Journal of Respiratory and Critical Care Medicine [American Thoracic Society]
卷期号:202 (4): 586-594 被引量:22
标识
DOI:10.1164/rccm.202003-0510oc
摘要

Rationale: Idiopathic and heritable pulmonary arterial hypertension (PAH) are rare but comprise a genetically heterogeneous patient group. RNA sequencing linked to the underlying genetic architecture can be used to better understand the underlying pathology by identifying key signaling pathways and stratify patients more robustly according to clinical risk. Objectives: To use a three-stage design of RNA discovery, RNA validation and model construction, and model validation to define a set of PAH-associated RNAs and a single summarizing RNA model score. To define genes most likely to be involved in disease development, we performed Mendelian randomization (MR) analysis. Methods: RNA sequencing was performed on whole-blood samples from 359 patients with idiopathic, heritable, and drug-induced PAH and 72 age- and sex-matched healthy volunteers. The score was evaluated against disease severity markers including survival analysis using all-cause mortality from diagnosis. MR used known expression quantitative trait loci and summary statistics from a PAH genome-wide association study. Measurements and Main Results: We identified 507 genes with differential RNA expression in patients with PAH compared with control subjects. A model of 25 RNAs distinguished PAH with 87% accuracy (area under the curve 95% confidence interval: 0.791–0.945) in model validation. The RNA model score was associated with disease severity and long-term survival (P = 4.66 × 10−6) in PAH. MR detected an association between SMAD5 levels and PAH disease susceptibility (odds ratio, 0.317; 95% confidence interval, 0.129–0.776; P = 0.012). Conclusions: A whole-blood RNA signature of PAH, which includes RNAs relevant to disease pathogenesis, associates with disease severity and identifies patients with poor clinical outcomes. Genetic variants associated with lower SMAD5 expression may increase susceptibility to PAH.
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
量子星尘发布了新的文献求助10
1秒前
星辰大海应助大橙子采纳,获得10
10秒前
10秒前
七QI完成签到 ,获得积分10
11秒前
14秒前
褚香旋完成签到,获得积分10
14秒前
一只狗东西完成签到 ,获得积分10
16秒前
宇老师发布了新的文献求助10
17秒前
18秒前
qiqi发布了新的文献求助30
20秒前
大橙子发布了新的文献求助10
23秒前
wzhang完成签到,获得积分10
24秒前
ken131完成签到 ,获得积分10
27秒前
myl完成签到,获得积分10
28秒前
728完成签到,获得积分10
34秒前
xiaofeng5838完成签到,获得积分10
34秒前
ronnie完成签到,获得积分10
34秒前
37秒前
寒冷芷蕊完成签到,获得积分20
37秒前
37秒前
Jane完成签到,获得积分10
37秒前
一氧化二氢完成签到,获得积分10
43秒前
凡事发生必有利于我完成签到,获得积分10
44秒前
yihaiqin完成签到 ,获得积分10
48秒前
轩辕剑身完成签到,获得积分0
48秒前
coolkid完成签到 ,获得积分0
49秒前
你怎么那么美完成签到,获得积分10
49秒前
游艺完成签到 ,获得积分10
52秒前
冬月完成签到 ,获得积分10
52秒前
薛乎虚完成签到 ,获得积分10
53秒前
54秒前
大胖完成签到,获得积分10
54秒前
野火197完成签到,获得积分10
58秒前
59秒前
量子星尘发布了新的文献求助10
1分钟前
April完成签到,获得积分10
1分钟前
周舟完成签到 ,获得积分10
1分钟前
V_I_G完成签到 ,获得积分10
1分钟前
nick完成签到,获得积分10
1分钟前
高高高完成签到 ,获得积分10
1分钟前
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
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
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 4038157
求助须知:如何正确求助?哪些是违规求助? 3575869
关于积分的说明 11373842
捐赠科研通 3305650
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022