Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study

孟德尔随机化 医学 内科学 痛风 优势比 冲程(发动机) 混淆 单核苷酸多态性 糖尿病 高尿酸血症 心脏病学 内分泌学 尿酸 基因型 遗传学 遗传变异 基因 工程类 生物 机械工程
作者
Tanya E. Keenan,Wei Zhao,Asif Rasheed,Weang-Kee Ho,Rainer Malik,Janine F. Felix,Robin Young,Nabi Shah,Maria Samuel,Nasir Sheikh,Megan Mucksavage,Omar J. Shah,Jin Li,Michael P. Morley,Annika Laser,Nadeem Hayat Mallick,Khan Shah Zaman,Mohammad Ishaq,Syed Zahed Rasheed,Fazal-ur-Rehman Memon,Faisal Ahmed,Bashir Hanif,Muhammad Shakir Lakhani,Muhammad Fahim,Madiha Ishaq,Naresh Kumar Shardha,Naveeduddin Ahmed,Khalid Mahmood,Waseem Iqbal,Saba Akhtar,Rabia Raheel,Christopher J. O’Donnell,Christian Hengstenberg,W. März,Sekar Kathiresan,Nilesh J. Samani,Anuj Goel,Jemma C. Hopewell,John C Chambers,Yu-Ching Cheng,Pankaj Sharma,Qiong Yang,Jonathan Rosand,Giorgio B. Boncoraglio,Shahana Urooj Kazmi,Håkon Håkonarson,Anna Köttgen,Andreas P. Kalogeropoulos,Philippe Frossard,Ayeesha Kamran Kamal,Martin Dichgans,Thomas P. Cappola,Muredach P. Reilly,John Danesh,Daniel J. Rader,Benjamin F. Voight,Danish Saleheen
出处
期刊:Journal of the American College of Cardiology [Elsevier BV]
卷期号:67 (4): 407-416 被引量:154
标识
DOI:10.1016/j.jacc.2015.10.086
摘要

Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain.Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF).This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls.Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations.Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.
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
宣以晴完成签到,获得积分10
刚刚
Nnn完成签到,获得积分10
1秒前
baby完成签到,获得积分10
4秒前
123完成签到,获得积分10
4秒前
5秒前
学术牛马完成签到,获得积分10
5秒前
sl发布了新的文献求助10
7秒前
完美的鹤完成签到,获得积分10
8秒前
hky完成签到,获得积分10
9秒前
TTTHANKS完成签到 ,获得积分10
10秒前
WW完成签到,获得积分10
10秒前
LL完成签到,获得积分10
11秒前
量子星尘发布了新的文献求助10
11秒前
小马的可爱老婆2完成签到,获得积分10
11秒前
缥缈纲完成签到,获得积分10
12秒前
TY完成签到 ,获得积分10
12秒前
迷路的小蚂蚁完成签到,获得积分10
13秒前
哈儿的跟班完成签到,获得积分10
13秒前
醉熏的鑫完成签到,获得积分20
14秒前
远_09完成签到 ,获得积分10
15秒前
网站技术人员完成签到,获得积分10
16秒前
eazin完成签到 ,获得积分10
17秒前
山野桃饼完成签到,获得积分10
17秒前
无私代芹完成签到,获得积分10
18秒前
画风湖湘卷完成签到,获得积分10
18秒前
段一帆完成签到,获得积分10
19秒前
结实的老虎完成签到,获得积分10
19秒前
19秒前
邓希静完成签到,获得积分10
20秒前
23秒前
24秒前
24秒前
26秒前
是冬天完成签到,获得积分10
27秒前
mengwensi完成签到,获得积分10
27秒前
单纯血茗发布了新的文献求助10
27秒前
胡大嘴先生完成签到,获得积分10
27秒前
林钟望完成签到,获得积分10
27秒前
碧蓝碧凡发布了新的文献求助10
28秒前
琴楼完成签到,获得积分10
31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 4038426
求助须知:如何正确求助?哪些是违规求助? 3576119
关于积分的说明 11374556
捐赠科研通 3305834
什么是DOI,文献DOI怎么找? 1819339
邀请新用户注册赠送积分活动 892678
科研通“疑难数据库(出版商)”最低求助积分说明 815029