Introduction
Growth-differentiation factor 15 (GDF15) is an inflammatory cytokine
involved in energy homeostasis1. Its circulating
levels are acutely increased by the type 2 diabetes medication
metformin, resulting in reduced appetite and weight
loss2. However, the effect of chronically elevated
circulating GDF15 levels on body weight is not known.
Here, we identified a genetic variant at the GDF15 gene to proxy
a small, lifelong increase in circulating GDF15 levels, and leveraged it
in genetic analyses to investigate the effects of chronically elevated
GDF15 levels on body mass index (BMI)
and type 2 diabetes liability.