Mendelian Randomization, 2nd Edition

7

Robust methods using variants from multiple gene regions

In this part of the book, we describe more advanced methods for Mendelian randomization. We begin by considering robust methods, which do not require all genetic variants to be valid instrumental variables (IVs) to give consistent estimates of a causal parameter.

If a particular gene region (or regions) has a specific biological link to the exposure, then we would generally advocate basing the primary Mendelian randomization analysis on variants from that region. However, particularly for complex risk factors such as body mass index or blood pressure, there is no single gene region that encodes the risk factor, and so a polygenic Mendelian randomization analysis is necessary. If ...