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In their letter, Hartwig and Davies1 raise an important issue that was not discussed in the original Mendelian randomization Egger regression (MR Egger) paper by Bowden et al.2 Hartwig and Davies point out that, similar to other varieties of MR, MR-Egger is also susceptible to weak instrument bias.
Background: Lean mass is positively associated with bone mineral density (BMD). However, the relationship between adiposity and BMD is more controversial. In particular, it is unclear if the observational association between the two reflects a causal effect of fat mass on BMD. Previous Mendelian randomization (MR) studies using variants in the FTO and MC4R genes as genetic instruments for adiposity have suggested that fat mass does indeed causally influence BMD.
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