Mendelian randomization studies in coronary artery disease

孟德尔随机化 生物标志物 医学 冠状动脉疾病 疾病 因果关系(物理学) 生物信息学 内科学 肿瘤科 基因型 遗传学 生物 基因 遗传变异 量子力学 物理
作者
Henning Jansen,Nilesh J. Samani,H. Schunkert
出处
期刊:European Heart Journal [Oxford University Press]
卷期号:35 (29): 1917-1924 被引量:207
标识
DOI:10.1093/eurheartj/ehu208
摘要

Epidemiological research over the last 50 years has discovered a plethora of biomarkers (including molecules, traits or other diseases) that associate with coronary artery disease (CAD) risk. Even the strongest association detected in such observational research precludes drawing conclusions about the causality underlying the relationship between biomarker and disease. Mendelian randomization (MR) studies can shed light on the causality of associations, i.e whether, on the one hand, the biomarker contributes to the development of disease or, on the other hand, the observed association is confounded by unrecognized exogenous factors or due to reverse causation, i.e. due to the fact that prevalent disease affects the level of the biomarker. However, conclusions from a MR study are based on a number of important assumptions. A prerequisite for such studies is that the genetic variant employed affects significantly the biomarker under investigation but has no effect on other phenotypes that might confound the association between the biomarker and disease. If this biomarker is a true causal risk factor for CAD, genotypes of the variant should associate with CAD risk in the direction predicted by the association of the biomarker with CAD. Given a random distribution of exogenous factors in individuals carrying respective genotypes, groups represented by the genotypes are highly similar except for the biomarker of interest. Thus, the genetic variant converts into an unconfounded surrogate of the respective biomarker. This scenario is nicely exemplified for LDL cholesterol. Almost every genotype found to increase LDL cholesterol level by a sufficient amount has also been found to increase CAD risk. Pending a number of conditions that needed to be fulfilled by the genetic variant under investigation (e.g. no pleiotropic effects) and the experimental set-up of the study, LDL cholesterol can be assumed to act as the functional component that links genotypes and CAD risk and, more importantly, it can be assumed that any modulation of LDL cholesterol—by whatever mechanism—would have similar effects on disease risk. Therefore, MR analysis has tremendous potential for identifying therapeutic targets that are likely to be causal for CAD. This review article discusses the opportunities and challenges of MR studies for CAD, highlighting several examples that involved multiple biomarkers, including various lipid and inflammation traits as well as hypertension, diabetes mellitus, and obesity.
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
zhx完成签到,获得积分10
刚刚
Knight-1124完成签到,获得积分20
刚刚
刚刚
MchemG应助qq采纳,获得10
1秒前
小二郎应助科研通管家采纳,获得10
1秒前
bkagyin应助科研通管家采纳,获得10
1秒前
1秒前
1秒前
Hello应助科研通管家采纳,获得10
1秒前
在水一方应助科研通管家采纳,获得10
1秒前
1秒前
SHAO应助科研通管家采纳,获得10
1秒前
pcr163应助科研通管家采纳,获得30
1秒前
1秒前
和谐一万完成签到,获得积分10
1秒前
SYLH应助科研通管家采纳,获得30
1秒前
quhayley应助科研通管家采纳,获得10
1秒前
Zhou发布了新的文献求助10
1秒前
科目三应助科研通管家采纳,获得10
1秒前
pcr163应助科研通管家采纳,获得30
2秒前
英姑应助科研通管家采纳,获得10
2秒前
Anita发布了新的文献求助10
2秒前
SYLH应助科研通管家采纳,获得10
2秒前
2秒前
我是老大应助科研通管家采纳,获得10
2秒前
SYLH应助科研通管家采纳,获得10
2秒前
Ava应助科研通管家采纳,获得10
2秒前
充电宝应助科研通管家采纳,获得10
2秒前
神的女人发布了新的文献求助10
2秒前
pcr163应助科研通管家采纳,获得30
2秒前
Liufgui应助科研通管家采纳,获得20
2秒前
褪黑素应助科研通管家采纳,获得10
2秒前
2秒前
2秒前
2秒前
2秒前
2秒前
2秒前
2秒前
SYLH应助科研通管家采纳,获得20
2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 3988732
求助须知:如何正确求助?哪些是违规求助? 3531027
关于积分的说明 11252281
捐赠科研通 3269732
什么是DOI,文献DOI怎么找? 1804764
邀请新用户注册赠送积分活动 881869
科研通“疑难数据库(出版商)”最低求助积分说明 809021