Results
Colocalization analysis within the GDF15 gene supported the model
with a shared causal genetic variant (posterior probability
> 0.99; Figure) for GDF15 levels and BMI, with rs16982345
identified as the most likely shared causal variant. In Mendelian
randomization analysis using the rs16982345 variant, genetically proxied
higher circulating GDF15 levels were associated with increased BMI
(change in standard deviation [SD] units per one SD increase in
GDF15 levels: 0.021 [95% confidence interval 0.014 to 0.028], p =\(4\times 10^{-9}\)). Exploring bi-directional effects, there was no
evidence of genetically proxied BMI being associated with GDF15 levels
(change in SD units per one SD increase in BMI: 0.005 [95% confidence
interval -0.133 to 0.143], p = 0.95). There was no strong evidence for
colocalization of GDF15 levels and type 2 diabetes liability (posterior
probability = 0.16).