Gene

World Wide Web

Health care

Biology

Actuarial science

Statistics

Causal inference

Body mass index

Economics

Mendelian randomization

Computer science

Genetics

Mathematics

Index (typography)

Genotype

Econometrics

Instrumental variable

Genetic variants

Medicine

Observational study

Economic growth

Pathology

Medical Decision Making

Causal effect estimates for the association of obesity with health care costs can be biased by reversed causation and omitted variables. In this study, we use genetic variants as instrumental variables to overcome these limitations, a method that is often called Mendelian randomization (MR). We describe the assumptions, available methods, and potential pitfalls of using genetic information and how to address them. We estimate the effect of body mass index (BMI) on total health care costs using data from a German observational study and from published large-scale data. In a meta-analysis of several MR approaches, we find that models using genetic instruments identify additional annual costs of €280 for a 1-unit increase in BMI. This is more than 3 times higher than estimates from linear regression without instrumental variables (€75). We found little evidence of a nonlinear relationship between BMI and health care costs. Our results suggest that the use of genetic instruments can be a powerful tool for estimating causal effects in health economic evaluation that might be superior to other types of instruments where there is a strong association with a modifiable risk factor.

Application of Mendelian Randomization to Investigate the Association of Body Mass Index with Health Care Costs