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Hum Mol Genet. 2014 Sep 15;23(R1):R89-98. doi: 10.1093/hmg/ddu328. Epub 2014 Jul 4.

Mendelian randomization: genetic anchors for causal inference in epidemiological studies.

Author information

1
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK Julia.Mackay@bristol.ac.uk.
2
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK.

Abstract

Observational epidemiological studies are prone to confounding, reverse causation and various biases and have generated findings that have proved to be unreliable indicators of the causal effects of modifiable exposures on disease outcomes. Mendelian randomization (MR) is a method that utilizes genetic variants that are robustly associated with such modifiable exposures to generate more reliable evidence regarding which interventions should produce health benefits. The approach is being widely applied, and various ways to strengthen inference given the known potential limitations of MR are now available. Developments of MR, including two-sample MR, bidirectional MR, network MR, two-step MR, factorial MR and multiphenotype MR, are outlined in this review. The integration of genetic information into population-based epidemiological studies presents translational opportunities, which capitalize on the investment in genomic discovery research.

PMID:
25064373
PMCID:
PMC4170722
DOI:
10.1093/hmg/ddu328
[Indexed for MEDLINE]
Free PMC Article

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