Network Mendelian Randomization Study Design to Assess Factors Mediating the Causal Link Between Telomere Length and Heart Disease.
نویسنده
چکیده
Mendelian randomization study designs represent new powerful tools available to researchers that enable causal inferences to be made about the effects of risk factors in health and disease outcomes in the context of a prospective observational study. These study designs involve estimating the association between a genetically modifiable risk factor and health and disease outcomes. If individuals with genetically lower or higher levels of a risk factor of interest are at greater or lesser risk of an outcome, then it can be inferred that the risk factor has a causal relationship to that outcome. Provided that a chosen genetic variant is strongly associated with the risk factor of interest, is not associated with other factors that might affect the risk factor, and imparts its influence on a given outcome exclusively through its link to the risk factor, these causal inferences are considered to be robust. Mendelian randomization study designs have become increasingly popular among epidemiologists in recent years as recently completed genome-wide association and genome sequencing studies have substantially increased our knowledge of the genetic factors associated with health and disease. Using Mendelian randomization techniques allows researchers to conduct studies that can make the kind of causal inferences that are typically only attainable from randomized controlled trials, thus avoiding much of expense, difficulty, and ethical issues that often arise with such trials. Furthermore, as demonstrated in an exciting recent publication in Circulation Research, titled Exploring the Causal Pathway from Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study by Zhan et al, these study designs allow assessment of the influence of risk factors that are impossible to manipulate in humans, like telomere length, on disease outcomes and the complex network of factors that mediate this influence.
منابع مشابه
Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study.
RATIONALE Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention. OBJECT...
متن کاملExploring the Causal Pathway From Telomere Length to Coronary Heart Disease
Telomeres are repetitive nucleotide sequences (TTAGGG)n at the end of chromosomes that protect the chromosomes from aberration or fusion with each other. Telomeres are shortened during each cell division and are proposed as biomarkers of cellular senescence and biological aging. Previous population-based observational studies found that shorter telomere length (TL) was associated with higher ri...
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BACKGROUND Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and triglyceride. The aim of this study was to ...
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A conventional Mendelian randomization analysis assesses the causal effect of a risk factor on an outcome by using genetic variants that are solely associated with the risk factor of interest as instrumental variables. However, in some cases, such as the case of triglyceride level as a risk factor for cardiovascular disease, it may be difficult to find a relevant genetic variant that is not als...
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Methods have been developed for Mendelian randomization that can obtain consistent causal estimates while relaxing the instrumental variable assumptions. These include multivariable Mendelian randomization, in which a genetic variant may be associated with multiple risk factors so long as any association with the outcome is via the measured risk factors (measured pleiotropy), and the MR-Egger (...
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عنوان ژورنال:
- Circulation research
دوره 121 3 شماره
صفحات -
تاریخ انتشار 2017