Journal
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 16
Volume 16, Issue -, Pages 327-350Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-genom-090314-050016
Keywords
causal analysis; structural equation modeling; genetic epidemiology; mining the phenome; pharmacogenomics
Categories
Funding
- Medical Research Council [MC_UU_12013/4, MC_UU_12013/1] Funding Source: researchfish
- MRC [MC_UU_12013/1, MC_UU_12013/4] Funding Source: UKRI
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Mendelian randomization (MR) is an approach that uses genetic variants associated with a modifiable exposure or biological intermediate to estimate the causal relationship between these variables and a medically relevant outcome. Although it was initially developed to examine the relationship between modifiable exposures/biomarkers and disease, its use has expanded to encompass applications in molecular epidemiology, systems biology, pharmacogenomics, and many other areas. The purpose of this review is to introduce MR, the principles behind the approach, and its limitations. We consider some of the new applications of the methodology, including informing drug development, and comment on some promising extensions, including two-step, two-sample, and bidirectional MR. We show how these new methods can be combined to efficiently examine causality in complex biological networks and provide a new framework to data mine high-dimensional studies as we transition into the age of hypothesis-free causality.
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