The challenge of Mendelian randomization approach

5. Mendelian randomization

Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization, the random assortment of genes from parents to offspring that occurs during gamete formation and conception provides one method for assessing the causal nature of so...

Pleiotropy-robust Mendelian randomization.

Background The potential of Mendelian randomization studies is rapidly expanding due to: (i) the growing power of genome-wide association study (GWAS) meta-analyses to detect genetic variants associated with several exposures; and (ii) the increasing availability of these genetic variants in large-scale surveys. However, without a proper biological understanding of the pleiotropic working of ge...

Fulfilling the promise of Mendelian randomization

Mendelian randomization in family data

The phrase "mendelian randomization" has become associated with the use of genetic polymorphisms to uncover causal relationships between phenotypic variables. The statistical methods useful in mendelian randomization are known as instrumental variable techniques. We present an approach to instrumental variable estimation that is useful in family data and is robust to the use of weak instruments...

Mendelian randomization as an instrumental variable approach to causal inference.

In epidemiological research, the causal effect of a modifiable phenotype or exposure on a disease is often of public health interest. Randomized controlled trials to investigate this effect are not always possible and inferences based on observational data can be confounded. However, if we know of a gene closely linked to the phenotype without direct effect on the disease, it can often be reaso...